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Purpose: This study aimed to assess changes in renal function during the acute disease and up to three months after the onset of symptoms among kidney transplant patients surviving COVID-19. Method(s): This ongoing single-center observational prospective study included kidney transplant recipients diagnosed between March 2020 and May 2021 and who survived the first 28 days. Before diagnosis, baseline renal function was defined as the mean of the last 3 creatinines. The follow-up period was 3 months. We used a one-way ANOVA test to compare the mean eGFR in baseline, 28 days, and 3 months after COVID-19. The CKD-EPI equation was used to estimate GFR. Result(s): Among the 787 patients, the mean age was 48.5 years, 59.3% were male, and 68.0% were white. Comorbidities as hypertension, diabetes and cardiopathy were present in 70.4%, 25.3%, and 3.9%, respectively. The mean body mass index was 26.9 kg/m2, and baseline GFR was 51,9 +/- 20.1 ml/min/1.73m2. Immunosuppression was reduced by 27.1% and suspended in 9.5% of cases. In 30.3% of the patients, acute kidney injury occurred, 7.8% needed dialysis support, and 2.5% had graft loss. There was a decline in renal function at 28 days (50.0 +/- 22.1 ml/min/1.73m2;p<0.001) and 3 months (47.3 +/- 21.0 ml/min/1.73m2;p<0.001) after COVID-19. Among the patients, 47.3% did not return to baseline eGFR values within three months and 19.9% had a reduction of at least 25% on renal function. Conclusion(s): COVID-19 does impact early renal function decline in KTR. These data reassure that KTR represent a group that benefits from early access to effective preventive strategies.
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Purpose: To evaluate the seroconversion rate in kidney transplant recipients (KTR), compared to two non-transplanted groups of patients, and identify predictors of seroconversion in COVID-19 convalescent patients. Method(s): A retrospective cohort study enrolled RT-PCR COVID-19 diagnosed patients (Mar/20 and Oct/2020) of three groups: 601 KTR, 211 health care workers (HCW), and 170 non-transplanted inhabitants (INH) in a countryside city in the state of Sao Paulo - Brazil. At least 14 days after diagnosis, all survivors underwent antibody testing by chemiluminescent microparticle immunoassay (titter expressed in RLU). The primary outcome was seroconversion. The group-adjusted multivariable model for the probability of seroconversion was built by generalized linear mixed models with binary logistic regression and the discrimination performance by AUC-ROC. Result(s): Several differences were observed among groups regarding demographic data and COVID-19 clinical presentation. Of note, KTR were older (54.0 years old vs. 37.0 in HCW vs. 42.0 in INH, P<0.001), more frequently had comorbidities (P<0.001), and severe COVID-19 (P<0.001). Compared to HCW and INH, respectively, admission to ICU (44.9% vs. 0% vs. 1.8%), MV requirement (32.3% vs. 0% vs. 1.8%), and death (28.8% vs. 0% vs. 1.2%) were significantly more frequent in KTR (P<0.001). On the other hand, the seroconversion rate was not different among survivors: 76.2% for KTR, 74.9% for HCW, and 82.2% for INH (P=0.35). The IgG anti-SARS-CoV-2 was slightly higher among INH: 5.8 RLU vs. 5.4 for KTR and 4.4 for HCW (P=0.009). Seroconversion was associated with a shorter time between infection and blood sample collection (OR for each day= 0.986;P<0.001) and increased by 64% if the fever was a COVID-19 symptom (OR=1.737;P=0.017), 78% if the cough was present (OR=1.785;P=0.005) and 98% if the ventilatory support was required (OR=1.981;P=0.017). This predictive model achieved an AU-ROC of 0.730 (P<0.001). Conclusion(s): As expected, the rates of clinical deterioration to ICU admission, MV requirement, and death were significantly higher among KTR. However, among the survivors, KTR had a similar rate of seroconversion, associated with clinical severity parameters and a shorter time of blood sample collection.
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Purpose: This study aims to compare the immunogenicity of a third dose of the heterologous BNT262b2 mRNA vaccine versus the homologous inactivated wholevirion CoronaVac vaccine in adult kidney transplant recipients (KTR). Method(s): This prospective, single-center, phase 4 interventional study included KTR aged 30-69 years, with more than 30days of transplantation, and no previous confirmed COVID-19. The patients received the 3rd heterologous (BNT162b2 mRNA) or homologous dose, at least four weeks after the standard two-dose schedule of CoronaVac vaccine, at the transplant center. Antibody response immediately before and after the 3rd dose was assessed by the AdviseDx SARS-CoV-2 IgG II assay. For those positive assays, neutralizing anti-SARS-CoV-2 antibodies were assessed through the cPassTM SARS-CoV-2 Neutralization Antibody Detection Kit. Result(s): There were 307 patients in the heterologous group and 777 patients in the homologous group. KTR in the heterologous group were older (median age 54 vs. 50 years,p<0.0001), with a lower prevalence of diabetes (7% vs. 11%,p=0.032), lower percentage of deceased donors (60% vs. 68%,p=0.006) and longer time since transplant (median 11 vs. 6 years,p< 0.0001).Immediately before the 3rd dose, seroprevalence for IgG antibodies (36% vs. 34%,p=0.597) and the median antibody titers among those seroprevalent (246 AU/mL vs. 268 AU/mL,p=0.279) were similar. At a median of 25 days after the heterologous and 35 days after the homologous 3rddose vaccine, seroconversion rate was higher in the heterologous group (49% vs. 32%,p<0.0001), resulting in a higher seroprevalence rate (67% vs. 55%,p=0.0003). Overall, 42% remained seronegative after the third dose. The median antibody titers after booster among those seroprevalent patients was higher in those in whom the 3rd heterologous vaccine was administered (7,771 AU/mL vs 599 AU/mL,p<0.0001). The analysis of the neutralizing activity is ongoing. Conclusion(s): This prospective interventional study suggests that a 3rd heterologous dose is associated with a higher seroconversion rate and median antibody titers compared to a homologous dose in kidney transplant recipients fully vaccinated with inactivated whole-virion CoronaVac vaccine. In addition, 42% of subjects did not produce humoral immune response after the third dose, urging the development of alternative strategies.
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Purpose: This study aimed to investigate the clinical consequences at 3 months after symptom onset among kidney transplant recipients surviving COVID-19. Method(s): This is an ongoing single-center observational prospective study including adult kidney transplant recipients who were diagnosed and survived after COVID-19 between 03/20/2020 and 05/31/2021. Patients who lost their graft were excluded. The patients are scheduled to receive a telephone contact at 3 months after symptom onset from the clinical research team. The call consisted of a structured questionnaire of symptoms with binary answers (yes or no). The questionnaire included the following symptoms: headache, dizziness, anosmia/ageusia, weakness, myalgia, inappetence, diarrhea, and dyspnea, which could be presented before and/or after the COVID-19 diagnosis. Those patients with at least one symptom presented only after the disease, were defined as having Long-COVID-19. Subsequently, the clinical research team included a question about the work status. Adjusted multivariable logistic regression models were used to identify the risk factors associated with Long-COVID-19. Result(s): There were 1,731 patients with COVID-19, with 455 deaths and 36 graft losses. Of the remaining 1,240 patients, 454 (36%) didn't answer our calls, yielding a final cohort of 786 patients. Of them, 217 (28%) developed Long-COVID-19. The incidence of each symptom at 3 months was: dyspnea (7%), myalgia (12%), weakness (11%), headache (10%), dizziness (7%), diarrhea (4%), inappetence (4%) and anosmia/ageusia (3%). About 1% of our patients needed domiciliary O2. Of those who we obtained the working status (n=239), 95 (40%) were employed before COVID-19 and 79 of them (83%) had returned to their original work at 3 months. After COVID-19 diagnosis, 44% of the patients were hospitalized (31% in ICU), 35% used supplemental O2, and 5% required mechanical ventilation. Fever (53%), shiver (39%), nausea (3%), anosmia/ageusia (59%), hospitalization (67%), and adverse cardiovascular events (3%), such as thrombosis or myocardial infarction, were risk factors associated with subsequent development of Long-COVID-19, using adjusted multivariable logistic regression. Conclusion(s): The incidence of Long-COVID-19 at 3 months was 28% and was associated with reduced quality of life and return to work. Several COVID-19 associated symptoms and disease severity markers were associated with Long- COVID-19.
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Purpose: A high number of comorbidities associated with the severity of the disease caused by SARS-CoV-2 (COVID-19) has been reported, such as systemic arterial hypertension (SAH), diabetes mellitus (DM), cerebrovascular and cardiovascular diseases, obesity, chronic kidney disease, among others. Importantly, poor glycemic control in diabetic individuals and hyperglycemia at admission are associated to COVID-19 progression. To evaluate whether kidney transplant recipients with DM have worse outcomes in COVID-19 setting when compared to non-diabetics, as well as to verify whether the poor glycemic control contributes to COVID-19 progression. Methods: Retrospective analyses of 590 kidney transplant recipients who were diagnosed with COVID-19 at one single Brazilian center. We used DM, SAH and poor glycemic control as dependent variables in univariate analyses to determinant the risk factors for COVID-19 progression. Results: 60% male, 64.4% white, average age 51.6 years-old, 192 (32.6%) DM and 158 (26.8%) SAH. COVID-19-related symptoms included: fever (63.4%), chills (63.4%), cough (60.3%), dyspnea (49.3%), myalgia (46.3 %), diarrhea (32.4%), anosmia (31.2%), headache (23.7%) and runny nose (21.7%). DM was associated with acute respiratory distress syndrome (ARDS) (P=0.0001), use of supplemental oxygen (P=0.001), intensive care unit (ICU) admission (P=0.0001), mechanical ventilation (MV) (P=0.001), acute graft dysfunction (P=0.0001), hemodialysis (P=0.009), and death (P=0.0001). Fasting blood glucose prior to hospitalization was related to the risk of death (130 vs 112 mg/dL, P=0.002), MV (130 vs 119 mg/ dl, P=0.0001) and ICU admission (127 vs 109 mg/dl, P=0.0001). HbA1c values were associated with the risk of MV (7.2 vs 6.9%, P =0.031) and ICU admission (7.1 vs 6.6%, P=0.025). SAH was associated with ARDS (P=0.044), ICU admission (P=0.028), MV (P=0.018), graft dysfunction (P=0.006), HD (P=0.007) and death (P=0.037). ACE inhibitors or ARBs were not associated with the risk of death (P=0.792 and P=0.138, respectively). Conclusions: DM and poor glycemic control, as well as SAH were associated with worse outcomes in COVID-19. These findings highlight the importance of adequate management of comorbidities in transplant patients, especially in relation to DM, since poor glycemic control contributes to the worst outcomes in COVID-19. ACE inhibitors and ARBs should not be discontinued during COVID-19 pandemic, as they do not increase the risk of death.
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OBJECTIVE: This study aims to describe the result of the strategies adopted to maintain the transplant program amid the COVID-19 pandemic. METHODS: Since March 2020, several measures have been adopted sequentially, including the compulsory use of personal protective equipment and the real-time polymerase chain reaction testing of collaborators, symptomatic patients, potential deceased donors, candidates for recipients, and in-hospital readmissions, regardless of symptoms. The living-donor transplantation was restricted to exceptional cases. RESULTS: Among 1013 health professionals, 201 cases of COVID-19 were confirmed between March and August 2020, with no severe cases reported. In this period, we observed a 19% institutional increase in the number of transplants from deceased donors compared with that observed in the same period in 2019. There was no donor-derived severe acute respiratory syndrome virus (SARS-CoV-2) infection. Four COVID-19-positive patients underwent transplantation;after 28 days, all were alive and with functioning allograft. Among the 11,875 already transplanted patients being followed up, there were 546 individuals with confirmed diagnosis, 372 who required hospitalization, and 167 on mechanical ventilation, resulting in a 27% mortality rate. CONCLUSIONS: These data confirm that the adoption of sequential and coordinated measures amid the pandemic was able to successfully maintain the transplant program and ensure the safety of health professionals and transplanted patients who were already in follow-up.
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INTRODUCTION: The unprecedented coronavirus disease 2019 (COVID-19) pandemic has affected kidney transplant (KT) recipients, with worldwide fatality rates around 25%. Considering the well-known Brazilian socio-demographic disparities, this report describes for the first time the main outcomes of COVID-19 in KT recipients according to Brazilian geographic regions. METHODS: This multicenter national retrospective analysis included data from KT recipients with confirmed COVID-19 between March and November 2020. RESULTS: Thirty-five of the 81 centers (57% of KT activity in Brazil) reported 1,680 patients with COVID-19. The Northeast was the first to reach the peak in the number of infections. The Southeast, due to its population density, contributed with the largest number of patients. Patients had a median age of 52 years, 76% had hypertension and 34% diabetes, 75% were recipients of a deceased donor, and the time interval between diagnosis and transplantation was 5.9 years. In 53% of patients, immunosuppression was adjusted, and clinical support varied according to geographic region. Hospitalization was required for 65% of the patients, 35% of them needed intensive care, 25% mechanical ventilation, and 23% renal replacement therapy. The 90-day overall fatality was 21%, being 23% in the Southeast, 16% in the Northeast, and 19% in the Central-west and South regions. CONCLUSION: The migratory pattern of the pandemic among KT recipients followed that of the general population and the outcomes were influenced by regional features. COVID-19 in KT recipients was associated with high utilization of health-care resources and higher fatality rates than those reported in the general population.