Changing trends in mortality among solid organ transplant recipients hospitalized for COVID-19 during the course of the pandemic

Mortality among patients hospitalized for COVID-19 has declined over the course of the pandemic. Mortality trends specifically in solid organ transplant recipients (SOTR) are unknown. Using data from a multicenter registry of SOTR hospitalized for COVID-19, we compared 28-day mortality between early 2020 (March 1, 2020–June 19, 2020) and late 2020 (June 20, 2020–December 31, 2020). Multivariable logistic regression was used to assess comorbidity-adjusted mortality. Time period of diagnosis was available for 1435/1616 (88.8%) SOTR and 971/1435 (67.7%) were hospitalized: 571/753 (75.8%) in early 2020 and 402/682 (58.9%) in late 2020 (p < .001). Crude 28-day mortality decreased between the early and late periods (112/571 [19.6%] vs. 55/402 [13.7%]) and remained lower in the late period even after adjusting for baseline comorbidities (aOR 0.67, 95% CI 0.46–0.98, p = .016). Between the early and late periods, the use of corticosteroids (≥6 mg dexamethasone/day) and remdesivir increased (62/571 [10.9%] vs. 243/402 [61.5%], p < .001 and 50/571 [8.8%] vs. 213/402 [52.2%], p < .001, respectively), and the use of hydroxychloroquine and IL-6/IL-6 receptor inhibitor decreased (329/571 [60.0%] vs. 4/492 [1.0%], p < .001 and 73/571 [12.8%] vs. 5/402 [1.2%], p < .001, respectively). Mortality among SOTR hospitalized for COVID-19 declined between early and late 2020, consistent with trends reported in the general population. The mechanism(s) underlying improved survival require further study.

     

Epidemiology and outcomes of medically attended and microbiologically confirmed bacterial foodborne infections in solid organ transplant recipients

Food-safety measures are recommended to solid organ transplant (SOT) recipients. However, the burden of foodborne infections in SOT recipients has not been established. We describe the epidemiology and outcomes of bacterial foodborne infections in a nationwide cohort including 4405 SOT recipients in Switzerland between 2008 and 2018. Participants were prospectively followed for a median of 4.2 years with systematic collection of data on infections, and patient and graft-related outcomes. We identified 151 episodes of microbiologically confirmed bacterial foodborne infections occurring in median 1.6 years (IQR 0.58–3.40) after transplantation (131 [88%] Campylobacter spp. and 15 [10%] non-typhoidal Salmonella). The cumulative incidence of bacterial foodborne infections was 4% (95% CI 3.4–4.8). Standardized incidence rates were 7.4 (95% CI 6.2–8.7) and 4.6 (95% CI 2.6–7.5) for Campylobacter and Salmonella infections, respectively. Invasive infection was more common with Salmonella (33.3% [5/15]) compared to Campylobacter (3.2% [4/125]; p = .001). Hospital and ICU admission rates were 47.7% (69/145) and 4.1% (6/145), respectively. A composite endpoint of acute rejection, graft loss, or death occurred within 30 days in 3.3% (5/151) of cases. In conclusion, in our cohort bacterial foodborne infections were late post-transplant infections and were associated with significant morbidity, supporting the need for implementation of food-safety recommendations.

     

Long-lasting cluster of nosocomial pneumonia with a single Pneumocystis jirovecii genotype involving different organ allograft recipients

Pneumocystis pneumonia (PCP) outbreaks may occur in solid organ transplant (SOT) patients. Transmissibility of Pneumocystis jirovecii among SOT and non-SOT patients has not been investigated. Ten SOT (ie, 4 heart, 4 kidney, 2 liver allograft recipients) and 11 non-SOT (ie, 7 HIV-infected, 3 hematologic malignancies, and 1 stem cell transplant) patients with PCP were admitted to London Health Sciences Center (LHSC) from October 2014 to August 2016. We investigated the course of illness and outcome of PCP in SOT and non-SOT patients. Post-transplant PCP was frequently an acute-onset disease (90% vs. 18.2%, p = .01) requiring ICU admission (70% vs. 20%, p = .03) and hemodialysis (60% vs. 0, p = .003). Mortality was more frequent in SOT patients (40% vs. 18.1%, p = .36). Multilocus sequence typing (MLST) demonstrated circulation of a single genotype of P. jirovecii among SOT patients. However, 8 different genotypes were detected from non-SOT patients. Reinstitution of prophylaxis successfully controlled post-transplant cluster until end of observation period in October 2019. No transmission was detected from non-SOT patients to SOT recipients. Detection of a single P. jirovecii genotype from all SOT recipients highlights the likelihood of nosocomial transmission. No source control method is recommended by current guidelines. Improvement of preventive strategies is required.     

Immunity to varicella,measles, and mumps in patients evaluated for lung transplantation

Vaccine-preventable viral infections are associated with increased risk of morbidity and mortality in post-transplant patients on immunosuppression regimens. Therefore, we studied rates of immunity against vaccine-preventable viruses in lung transplantation (LTx) candidates and their associations with underlying lung disease and clinical characteristics. We retrospectively studied 1025 consecutive adult patients who underwent first-time evaluation for LTx at a single center between January 2016 and October 2018. Viruses studied included varicella zoster (VZV), measles, and mumps. Young age (17–48 years old) was negatively associated with immunity for VZV (OR 4.54, p < .001), measles (OR 15.45, p < .001) and mumps (OR 3.1, p < .001), as compared to those 65+. Many LTx candidates with cystic fibrosis (CF) had undetectable virus-specific antibody titers including: 13.5% for VZV, 19.1% for measles, and 15.7% for mumps with significant odds of undetectable titers for VZV (OR 4.54, p < .001) and measles (OR 2.32, p = .010) as compared to those without CF. Therefore, a substantial number of patients undergoing LTx evaluation had undetectable virus-specific antibody titers. Our results emphasize the importance of screening for immunity to vaccine-preventable infections in this population and the need for revaccination in selected patients to boost their humoral immunity prior to transplantation.

     

An early experience on the effect of solid organ transplant status on hospitalized COVID-19 patients

We compared the outcome of COVID-19 in immunosuppressed solid organ transplant (SOT) patients to a transplant naïve population. In total, 10 356 adult hospital admissions for COVID-19 from March 1, 2020 to April 27, 2020 were analyzed. Data were collected on demographics, baseline clinical conditions, medications, immunosuppression, and COVID-19 course. Primary outcome was combined death or mechanical ventilation. We assessed the association between primary outcome and prognostic variables using bivariate and multivariate regression models. We also compared the primary endpoint in SOT patients to an age, gender, and comorbidity-matched control group. Bivariate analysis found transplant status, age, gender, race/ethnicity, body mass index, diabetes, hypertension, cardiovascular disease, COPD, and GFR <60 mL/min/1.73 m² to be significant predictors of combined death or mechanical ventilation. After multivariate logistic regression analysis, SOT status had a trend toward significance (odds ratio [OR] 1.29; 95% CI 0.99–1.69, p = .06). Compared to an age, gender, and comorbidity-matched control group, SOT patients had a higher combined risk of death or mechanical ventilation (OR 1.34; 95% CI 1.03–1.74, p = .027).     

Epidemiology and long-term outcomes of cytomegalovirus DNAemia and disease in pediatric solid organ transplant recipients

Despite prevention strategies, cytomegalovirus (CMV) remains a common infection in pediatric solid organ transplant recipients (SOTR). We sought to determine the frequency, associations with, and long-term outcomes of CMV DNAemia in pediatric SOTR. We performed a single-center retrospective cohort study, including 687 first time SOTR ≤21 years receiving universal prophylaxis from 2011 to 2018. Overall, 159 (23%) developed CMV DNAemia, the majority occurring after completing primary prophylaxis. CMV disease occurred in 33 (5%) SOTR, 25 (4%) with CMV syndrome and 10 (1%) with proven/probable tissue-invasive disease. CMV contributed to the death of three (0.4%) patients (all lung). High-risk (OR 6.86 [95% CI, 3.6–12.9]) and intermediate-risk (4.36 [2.3–8.2]) CMV status and lung transplantation (4.63 [2.33–9.2]) were associated with DNAemia on multivariable analysis. DNAemia was associated with rejection in liver transplant recipients (p < .01). DNAemia was not associated with an increase in graft failure, all-cause mortality, or other organ-specific poor outcomes. We report one of the lowest rates of CMV disease after SOTR, showing that universal prophylaxis is effective and should be continued. However, we observed CMV morbidity and mortality in a subset of patients, highlighting the need for research on optimal prevention strategies. This study was IRB approved.

     

A randomized controlled trial of liposomal cyclosporine A for inhalation in the prevention of bronchiolitis obliterans syndrome following lung transplantation

Long-term survival after lung transplantation is limited by chronic allograft dysfunction. The aim of this study was to investigate the effect of locally augmented immunosuppression with liposomal cyclosporine A for inhalation (L-CsA-i) for the prevention of bronchiolitis obliterans syndrome (BOS). In a randomized, double-blind, placebo-controlled, multi-center Phase 3 study, 180 LT recipients in BOS grade 0 were planned to receive L-CsA-i or placebo in addition to triple-drug immunosuppression. L-CsA-i was administered twice daily via an Investigational eFlow nebulizer to recipients of single (SLT) and bilateral lung transplants (BLT) within 6–32 weeks posttransplant, and continued for 2 years. The primary endpoint was BOS-free survival. 130 patients were enrolled before the study was prematurely terminated for business reasons. Despite a 2-year actuarial difference in BOS-free survival of 14.1% in favor of L-CsA-i in the overall study population, the primary endpoint was not met (p = .243). The pre-defined per protocol analysis of SLT recipients (n = 24) resulted in a treatment difference of 58.2% (p = .053). No difference was observed in the BLT (n = 48) subpopulation (p = .973). L-CsA-i inhalation was well tolerated. Although this study failed to meet its primary endpoint, the results warrant additional investigation of L-CsA-i in lung transplant recipients.

     

Joint modeling of liver transplant candidates outperforms the model for end-stage liver disease: The effect of disease development over time on patient outcome

Liver function is measured regularly in liver transplantation (LT) candidates. Currently, these previous disease development data are not used for survival prediction. By constructing and validating joint models (JMs), we aimed to predict the outcome based on all available data, using both disease severity and its rate of change over time. Adult LT candidates listed in Eurotransplant between 2007 and 2018 (n = 16 283) and UNOS between 2016 and 2019 (n = 30 533) were included. Patients with acute liver failure, exception points, or priority status were excluded. Longitudinal MELD(-Na) data were modeled using spline-based mixed effects. Waiting list survival was modeled with Cox proportional hazards models. The JMs combined the longitudinal and survival analysis. JM 90-day mortality prediction performance was compared to MELD(-Na) in the validation cohorts. MELD(-Na) score and its rate of change over time significantly influenced patient survival. The JMs significantly outperformed the MELD(-Na) score at baseline and during follow-up. At baseline, MELD-JM AUC and MELD AUC were 0.94 (0.92–0.95) and 0.87 (0.85–0.89), respectively. MELDNa-JM AUC was 0.91 (0.89–0.93) and MELD-Na AUC was 0.84 (0.81–0.87). The JMs were significantly (p < .001) more accurate than MELD(-Na). After 90 days, we ranked patients for LT based on their MELD-Na and MELDNa-JM survival rates, showing that MELDNa-JM-prioritized patients had three times higher waiting list mortality.

     

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.     

COVID-19 in solid organ transplant recipients: a single-center experience

Solid organ transplant (SOT) recipients may be at risk for severe COVID-19. Data on the clinical course of COVID-19 in immunosuppressed patients are limited, and the effective treatment strategy for these patients is unknown. We describe our institutional experience with COVID-19 in SOT. Demographic, clinical, and treatment data were extracted from the electronic patient files. A total of 23 SOT transplant recipients suffering from COVID-19 were identified (n = 3 heart; n = 15 kidney; n = 1 kidney-after-heart; n = 3 lung, and n = 1 liver transplant recipient). The presenting symptoms were similar to nonimmunocompromised patients. Eighty-three percent (19/23) of the patients required hospitalization, but only two of these were transferred to the intensive care unit. Five patients died from COVID-19; all had high Clinical Frailty Scores. In four of these patients, mechanical ventilation was deemed futile. In 57% of patients, the immunosuppressive therapy was not changed and only three patients were treated with chloroquine. Most patients recovered without experimental antiviral therapy. Modification of the immunosuppressive regimen alone could be a therapeutic option for SOT recipients suffering from moderate to severe COVID-19. Pre-existent frailty is associated with death from COVID-19.     

Liver transplantation from active COVID-19 donors: A lifesaving opportunity worth grasping?

COVID-19 pandemic dramatically impacted transplantation landscape. Scientific societies recommend against the use of donors with active SARS-CoV-2 infection. Italian Transplant Authority recommended to test recipients/donors for SARS-CoV-2-RNA immediately before liver transplant (LT) and, starting from November 2020, grafts from deceased donors with active SARS-CoV-2 infection were allowed to be considered for urgent-need transplant candidates with active/resolved COVID-19. We present the results of the first 10 LTs with active COVID-19 donors within an Italian multicenter series. Only two recipients had a positive molecular test at LT and one of them remained positive up to 21 days post-LT. None of the other eight recipients was found to be SARS-CoV-2 positive during follow-up. IgG against SARS-CoV-2 at LT were positive in 80% (8/10) of recipients, and 71% (5/7) showed neutralizing antibodies, expression of protective immunity related to recent COVID-19. In addition, testing for SARS-CoV-2 RNA on donors’ liver biopsy at transplantation was negative in 100% (9/9), suggesting a very low risk of transmission with LT. Immunosuppression regimen remained unchanged, according to standard protocol. Despite the small number of cases, these data suggest that transplanting livers from donors with active COVID-19 in informed candidates with SARS-CoV-2 immunity, might contribute to safely increase the donor pool.

     

Prevalence and predictors of SARS-CoV-2 antibodies among solid organ transplant recipients with confirmed infection

It remains uncertain whether immunocompromised patients including solid organ transplant (SOT) recipients will have a robust antibody response to SARS-CoV-2 infection. We enrolled all adult SOT recipients at our center with confirmed SARS-CoV-2 infection who underwent antibody testing with a single commercially available anti-nucleocapsid antibody test at least 7 days after diagnosis in a retrospective cohort. Seventy SOT recipients were studied (56% kidney, 19% lung, 14% liver ± kidney, and 11% heart ± kidney recipients). Thirty-six (51%) had positive anti-nucleocapsid antibody testing, and 34 (49%) were negative. Recipients of a kidney allograft were less likely to have positive antibody testing compared to those who did not receive a kidney (p = .04). In the final multivariable model, the years from transplant to diagnosis (OR 1.26, p = .002) and baseline immunosuppression with more than two agents (OR 0.26, p = .03) were significantly associated with the antibody test result, controlling for kidney transplantation. In conclusion, among SOT recipients with confirmed infection, only 51% of patients had detectable anti-nucleocapsid antibodies, and transplant-related variables including the level and nature of immunosuppression were important predictors. These findings raise the concern that SOT recipients with COVID-19 may be less likely to form SARS-CoV-2 antibodies.     

Bacteremia in solid organ transplant recipients as compared to immunocompetent patients: Acute phase cytokines and outcomes in a prospective,matched cohort study

We undertook a prospective, matched cohort study of patients with Staphylococcus aureus bacteremia (SAB) and gram-negative bacteremia (GNB) to compare the characteristics, outcomes, and chemokine and cytokine response in transplant recipients to immunocompetent, nontransplant recipients. Fifty-five transplant recipients (GNB n = 29; SAB n = 26) and 225 nontransplant recipients (GNB n = 114; SAB n = 111) were included for clinical analysis. Transplant GNB had a significantly lower incidence of septic shock than nontransplant GNB (10.3% vs 30.7%, p = .03). Thirty-day mortality did not differ significantly between transplant and nontransplant recipients with GNB (10.3% vs 15.8%, p = .57) or SAB (0.0% vs 11.7%, p = .13). Next, transplant patients were matched 1:1 with nontransplant patients for the chemokine and cytokine analysis. Five cytokines and chemokines were significantly lower in transplant GNB vs nontransplant GNB: IL-2 (median [IQR]: 7.1 pg/ml [7.1, 7.1] vs 32.6 pg/ml [7.1, 88.0]; p = .001), MIP-1β (30.7 pg/ml [30.7, 30.7] vs 243.3 pg/ml [30.7, 344.4]; p = .001), IL-8 (32.0 pg/ml [5.6, 53.1] vs 59.1 pg/ml [39.2, 119.4]; p = .003), IL-15 (12.0 pg/ml [12.0, 12.0] vs 12.0 pg/ml [12.0, 126.7]; p = .03), and IFN-α (5.1 pg/mL [5.1, 5.1] vs 5.1 pg/ml [5.1, 26.3]; p = .04). Regulated upon Activation, Normal T Cell Expressed and Secreted (RANTES) was higher in transplant SAB vs nontransplant SAB (mean [SD]: 750.2 pg/ml [194.6] vs 656.5 pg/ml [147.6]; p = .046).     

Changes and mediators of survival disparity among Black liver transplant recipients in the United States

A landmark 2002 study identified Black liver transplant (LT) recipients as having lower post-LT survival compared to other races. While persistent disparities exist, changes over time and mediating factors are understudied. Capturing LT recipients between 2002 and 2018 in UNOS, we used logistic regression and Cox proportional-hazard models to calculate differences in post-LT mortality among races. We examined interactions between transplant year and race. A mediation analysis assessed biologic and environmental factors potentially associated with race differences in post-LT survival. The cohort included 46,997 LT recipients (3898 Black;36,560 White;6539 Hispanic). In most years, Black (vs. White) LT recipients had a higher probability of age-adjusted mortality, not observed among Hispanics. In multivariable analysis, Blacks (vs. Whites) had higher (aHR = 1.15, 95% CI 1.07–1.24), whereas Hispanics had lower (aHR = 0.78, 95% CI 0.72–0.83) risk of mortality. Differences in post-LT mortality among Blacks (vs. Whites) narrowed between 2002 and 2009, were similar between 2010 and 2013, and may have worsened between 2014 and 2018. Race differences were larger for mortality beyond 1-year post-LT (vs. within 1-year), and among non-HCV (vs. HCV). Alcohol-associated liver disease (ALD) was the strongest mediator (13.9%, 95% CI 8.7–32.7%) of the Black–White disparity in 2010–2018. Our analyses suggest disparities may worsen with longer follow-up, as HCV recedes with elimination efforts, and with further increases in ALD.

     

Graft-versus-host disease after liver transplantation is associated with bone marrow failure,hemophagocytosis, and DNMT3A mutations

Graft-versus-host disease after liver transplantation (LT-GVHD) is rare, frequently fatal, and associated with bone marrow failure (BMF), cytopenias, and hyperferritinemia. Given hyperferritinemia and cytopenias are present in hemophagocytic lymphohistiocytosis (HLH), and somatic mutations in hematopoietic cells are associated with hyperinflammatory responses (clonal hematopoiesis of indeterminate potential, CHIP), we identified the frequency of hemophagocytosis and CHIP mutations in LT-GVHD. We reviewed bone marrow aspirates and biopsies, quantified blood/marrow chimerism, and performed next-generation sequencing (NGS) with a targeted panel of genes relevant to myeloid malignancies, CHIP, and BMF. In all, 12 marrows were reviewed from 9 LT-GVHD patients. In all, 10 aspirates were evaluable for hemophagocytosis; 7 had adequate DNA for NGS. NGS was also performed on marrow from an LT cohort (n = 6) without GVHD. Nine of 10 aspirates in LT-GVHD patients showed increased hemophagocytosis. Five (71%) of 7 with LT-GVHD had DNMT3A mutations; only 1 of 6 in the non-GVHD LT cohort demonstrated DNMT3A mutation (p = .04). Only 1 LT-GVHD patient survived. BMF with HLH features was associated with poor hematopoietic recovery, and DNMT3A mutations were over-represented, in LT-GVHD patients. Identification of HLH features may guide prognosis and therapeutics. Further studies are needed to clarify the origin and impact of CHIP mutations on the hyperinflammatory state.

     

Cellular and humoral immune response after mRNA-1273 SARS-CoV-2 vaccine in liver and heart transplant recipients

Recently published studies have found an impaired immune response after SARS-CoV-2 vaccination in solid organ recipients. However, most of these studies have not assessed immune cellular responses in liver and heart transplant recipients. We prospectively studied heart and liver transplant recipients eligible for SARS-CoV-2 vaccination. Patients with past history of SARS-CoV-2 infection or SARS-CoV-2 detectable antibodies (IgM or IgG) were excluded. We assessed IgM/IgG antibodies and ELISpot against the S protein 4 weeks after receiving the second dose of the mRNA-1273 (Moderna) vaccine. Side effects, troponin I, liver tests and anti-HLA donor-specific antibodies (DSA) were also assessed. A total of 58 liver and 46 heart recipients received two doses of mRNA-1273 vaccine. Median time from transplantation to vaccination was 5.4 years (IQR 0.3–27). Sixty-four percent of the patients developed SARS-CoV-2 IgM/IgG antibodies and 79% S-ELISpot positivity. Ninety percent of recipients developed either humoral or cellular response (87% in heart recipients and 93% in liver recipients). Factors associated with vaccine unresponsiveness were hypogammaglobulinemia and vaccination during the first year after transplantation. Local and systemic side effects were mild or moderate, and none presented DSA or graft dysfunction after vaccination. Ninety percent of our patients did develop humoral or cellular responses to mRNA-1273 vaccine. Factors associated with vaccine unresponsiveness were hypogammaglobulinemia and vaccination during the first year after transplantation, highlighting the need to further protect these patients.

     

Usefulness of a systematic approach at listing for vaccine prevention in solid organ transplant candidates

Solid organ transplant (SOT) candidates may not be immune against potentially vaccine‐preventable diseases because of insufficient immunizations and/or limited vaccine responses. We evaluated the impact on vaccine immunity at transplant of a systematic vaccinology workup at listing that included (1) pneumococcal with and without influenza immunization, (2) serology‐based vaccine recommendations against measles, varicella, hepatitis B virus, hepatitis A virus, and tetanus, and (3) the documentation of vaccines and serology tests in a national electronic immunization registry ( www.myvaccines.ch ). Among 219 SOT candidates assessed between January 2014 and November 2015, 54 patients were transplanted during the study. Between listing and transplant, catch‐up immunizations increased the patients’ immunity from 70% to 87% (hepatitis A virus, P = .008), from 22% to 41% (hepatitis B virus, P = .008), from 77% to 91% (tetanus, P = .03), and from 78% to 98% (Streptococcus pneumoniae, P = .002). Their immunity at transplant was significantly higher against S. pneumoniae (P = .006) and slightly higher against hepatitis A virus (P = .07), but not against hepatitis B virus, than that of 65 SOT recipients transplanted in 2013. This demonstrates the value of a systematic multimodal serology‐based approach of immunizations of SOT candidates at listing and the need for optimized strategies to increase their hepatitis B virus vaccine responses.     

Clinical implications of SARS-CoV-2 cycle threshold values in solid organ transplant recipients

Detection of SARS-CoV-2 viral RNA by RT-PCR assays is the primary diagnostic test for COVID-19. Cycle threshold (C_T) values generated by some of these assays provide inversely proportional proxy measurements of viral load. The clinical implications of C_T values are incompletely characterized, particularly in solid organ transplant (SOT) recipients. We conducted a retrospective chart review of 25 adult SOT recipients admitted to the Yale New Haven Health System between March 1 and May 15, 2020, analyzing 50 test results to investigate the clinical implications of SARS-CoV-2 C_T values in this population. Initial C_T values from upper respiratory tract samples were significantly higher in patients on tacrolimus, but were not associated with admission severity nor highest clinical acuity. Viral RNA was detected up to 38 days from symptom onset with a gradual increase in C_T values over time. In five patients with serial testing, C_T values <35.0 were detected >21 days after symptom onset in 4/5 and ≥27 days in 2/5, demonstrating prolonged RNA detection. These data describe SARS-CoV-2 viral dynamics in SOT patients and suggest that C_T values may not be useful to predict COVID-19 severity in SOT patients. SARS-CoV-2 C_T values may be more useful in informing infection prevention measures.     

Humoral response to SARS-CoV-2 is well preserved and symptom dependent in kidney transplant recipients

Data on the immune response to SARS-CoV-2 in kidney transplant recipients are scarce. Thus, we conducted a single-center observational study to assess the anti-SARS-CoV-2 IgG seroprevalence in outpatient kidney transplant recipients (KTR; n = 1037) and healthcare workers (HCW; n = 512) during the second wave of the COVID-19 pandemic in fall 2020 and evaluated the clinical variables affecting antibody levels. Antibodies against S1 and S2 subunit of SARS-CoV-2 were evaluated using immunochemiluminescent assay (cut off 9.5 AU/ml, sensitivity of 91.2% and specificity of 90.2%). Anti-SARS-CoV-2 IgG seroprevalence was lower in KTR than in HCW (7% vs. 11.9%, p = .001). Kidney transplant recipients with SARS-CoV-2 infection were younger (p = .001) and received CNI-based immunosuppression more frequently (p = .029) than seronegative KTR. Anti-SARS-CoV-2 IgG positive symptomatic KTR had a higher BMI (p = .04) than asymptomatic KTR. Interestingly, anti-SARS-CoV-2 IgG levels were higher in KTR than in HCW (median 31 AU/ml, IQR 17–84 vs. median 15 AU/ml, IQR 11–39, p < .001). The presence of moderate to severe symptoms in KTR was found to be the only independent factor affecting IgG levels (Beta coefficient = 41.99, 95% CI 9.92–74.06, p = .011) in the multivariable model. In conclusion, KTR exhibit a well-preserved symptom-dependent humoral response to SARS-CoV-2 infection.