High Prevalence of Long-COVID Among Kidney Transplant Recipients: A Longitudinal Cohort Study.

BACKGROUND: Kidney transplant recipients are at a higher risk to develop more severe clinical forms of coronavirus disease 2019 (COVID-19), perhaps increasing the risk of presenting its long-term clinical complications, labeled as Long-COVID. METHODS: This single-center, observational, prospective study included adult kidney transplant recipients with COVID-19 confirmed by reverse transcription polymerase chain reaction between March 20, 2020, and May 31, 2021, who were alive and with functioning graft 3 mo after the onset of symptoms. The prevalence of Long-COVID was investigated by a phone survey using a structured questionnaire of organic symptoms. Adjusted multivariable logistic regression models were used to investigate independent risk factors. RESULTS: Of 1741 patients who developed COVID-19, 465 died, and 37 returned to dialysis. Of the 1239 eligible patients, 780 (63%) answered the survey during the window period. The mean age was 48 ± 12 y, 41% were women, and the mean time from transplantation was 8 ± 6 y. During acute illness, 45% needed hospitalization. Long-COVID was identified in 214 (27%) of the subjects, with body aches being the most prevalent symptom (44%). Of 233 who provided working status, 17% did not return to work within 3 mo. No baseline characteristics or infection-related variables predicted Long-COVID; actually, the number of symptoms in the acute illness was the only independent risk factor identified (hazard ratio, 1.12; 95% confidence interval, 1.02-1.22). CONCLUSION: In this cohort of kidney transplant recipients, Long-COVID was prevalent and associated with a reduced return to work. The burden of acute phase symptoms was the only risk factor associated with Long-COVID.

The Mycophenolate-based Immunosuppressive Regimen Is Associated With Increased Mortality in Kidney Transplant Patients With COVID-19.

BACKGROUND: The chronic use of immunosuppressive drugs is a key risk factor of death because of coronavirus disease 2019 (COVID-19) in kidney transplant recipients (KTRs), although no evident association between the class of immunosuppressive and outcomes has been observed. Thus, we aimed to compare COVID-19-associated outcomes among KTRs receiving 3 different immunosuppressive maintenance regimes. METHODS: This study included data from 1833 KTRs with COVID-19 diagnosed between March 20 and April 21 extracted from the national registry before immunization. All patients were taking calcineurin inhibitor associated with mycophenolate acid (MPA, n = 1258), azathioprine (AZA, n = 389), or mammalian targets of rapamycin inhibitors (mTORi, n = 186). Outcomes within 30 and 90 d were assessed. RESULTS: Compared with patients receiving MPA, the 30-d (79.9% versus 87.9% versus 89.2%; P < 0.0001) and 90-d (75% versus 83.5% versus 88.2%; P < 0.0001) unadjusted patient survivals were higher in those receiving AZA or mTORi, respectively. Using adjusted multivariable Cox regression, compared with patients receiving AZA, the use of MPA was associated with a higher risk of death within 30 d (adjusted hazard ratio [aHR], 1.70; 95% confidence interval [CI], 1.21-2.40; P = 0.003), which was not observed in patients using mTORi (aHR, 0.78; 95% CI, 0.45-1.35; P = 0.365). At 90 d, although higher risk of death was confirmed in patients receiving MPA (aHR, 1.46; 95% CI, 1.09-1.98; P = 0.013), a reduced risk was observed in patients receiving mTORi (aHR, 0.59; 95% CI, 0.35-0.97; P = 0.04) compared with AZA. CONCLUSIONS: This national cohort data suggest that, in KTRs receiving calcineurin inhibitor and diagnosed with COVID-19, the use of MPA was associated with higher risk of death, whereas mTORi use was associated with lower risk of death.

Immunogenicity After a Heterologous BNT262b2 Versus Homologous Booster in Kidney Transplant Recipients Receiving 2 Doses of CoronaVac Vaccine: A Prospective Cohort Study.

BACKGROUND: Comparative studies of third heterologous doses following the CoronaVac vaccine against coronavirus disease 2019 (COVID-19) in kidney transplant recipients are lacking. METHODS: This prospective, single-center cohort study included kidney transplant recipients without previous COVID-19. Patients received a third heterologous (BNT162b2 mRNA) or homologous dose at least 4 wk after 2 doses of the CoronaVac vaccine. Immunoglobulin G antibody response and seroprevalence for neutralizing anti-severe acute respiratory syndrome coronavirus 2 antibodies immediately before and 28 d after third doses were compared between the groups. RESULTS: There were 307 patients in the heterologous group and 777 in the homologous group. Patients in the heterologous group were older (54 versus 50 y; P < 0.0001), with a longer time since transplant (11 versus 6 y; P < 0.0001). Immediately before the third dose, immunoglobulin G seroprevalence (36% versus 34%; P = 0.597) and antibody titers (246 versus 268 AU/mL; P = 0.279) were similar. After booster, seroconversion was higher in the heterologous group (49% versus 32%; P < 0.0001), resulting in a higher seroprevalence (67% versus 55%; P = 0.0003); however, 42% of all patients remained seronegative. Antibody titers after booster in seropositive patients were higher in the heterologous group (7771 versus 599 AU/mL; P < 0.0001). These results persisted after adjusting for confounding variables. Lastly, a similar proportion of patients became seropositive for neutralizing antibodies (98% versus 94%; P = 0.098). CONCLUSIONS: In kidney transplant recipients fully vaccinated with CoronaVac, a third dose with an mRNA vaccine produced a higher seroconversion rate and antibody titers than a third homologous dose. However, both boosters achieved equivalent seroprevalence for neutralizing antibodies. The high proportion of still seronegative patients indicates the need for alternative strategies of protection.

Temporal Reduction in COVID-19-Associated Fatality Among Kidney Transplant Recipients: The Brazilian COVID-19 Registry Cohort Study.

Data from the general population suggest that fatality rates declined during the course of the pandemic. This analysis, using data extracted from the Brazilian Kidney Transplant COVID-19 Registry, seeks to determine fatality rates over time since the index case on March 3rd, 2020. Data from hospitalized patients with RT-PCR positive SARS-CoV-2 infection from March to August 2020 (35 sites, 878 patients) were compared using trend tests according to quartiles (Q1: <72 days; Q2: 72-104 days; Q3: 105-140 days; Q4: >140 days after the index case). The 28-day fatality decreased from 29.5% (Q1) to 18.8% (Q4) (pfor-trend = 0.004). In multivariable analysis, patients diagnosed in Q4 showed a 35% reduced risk of death. The trend of reducing fatality was associated with a lower number of comorbidities (20.7-10.6%, p for-trend = 0.002), younger age (55-53 years, pfor-trend = 0.062), and better baseline renal function (43.6-47.7 ml/min/1.73 m2, pfor-trend = 0.060), and were confirmed by multivariable analysis. The proportion of patients presenting dyspnea (pfor-trend = 0.001) and hypoxemia (pfor-trend < 0.001) at diagnosis, and requiring intensive care was also found reduced (pfor-trend = 0.038). Despite possible confounding variables and time-dependent sampling differences, we conclude that COVID-19-associated fatality decreased over time. Differences in demographics, clinical presentation, and treatment options might be involved.

Inactivated Whole-virus Vaccine Triggers Low Response Against SARS-CoV-2 Infection Among Renal Transplant Patients: Prospective Phase 4 Study Results.

BACKGROUND: Anti-severe acute respiratory syndrome coronavirus 2 mRNA vaccines elicit lower humoral responses in solid-organ transplant recipients. This is the first prospective trial investigating the effect of an inactivated whole-virion vaccine in kidney transplant recipients. METHODS: Prospective, single-center, phase 4, interventional study. Kidney transplant recipients aged 30-69 y with >30 d of transplantation received two 3 µg intramuscular doses of CoronaVac 28 d apart and are being followed for 6 mo. Primary outcomes: (1) reactogenicity after first dose; (2) antibody responses 28 d after each dose; and (3) incidence/severity of confirmed coronavirus disease 2019 (COVID-19) and 28-d lethality rate. For this analysis, clinical effectiveness was assessed for 3 mo, starting 15 d after the second dose, and compared with 3-mo period before vaccination. RESULTS: Of the 3371 individuals who received the first dose, 99% completed vaccination schedule. Mild/local adverse reactions were reported by 33% of the patients. In the immunogenicity cohort (n = 942), the proportion of patients with IgG antibodies to severe acute respiratory syndrome coronavirus 2 increased from 15.2% after first dose to 43% after second dose. Increase in antibody values after second dose was associated with higher proportion of patients with detected neutralizing antibodies. A significant reduction in the incidence of COVID-19 was observed (6.4% versus 4.2%; P < 0.0001), although the 28-d lethality rate remained unchanged (25% versus 22%; P = 0.534). In 45 patients from the immunogenicity cohort who developed COVID-19, all the 6 deaths occurred among those without antibody response (n = 22; 49%). CONCLUSIONS: CoronaVac vaccine was associated with low reactogenicity, low immunogenicity but reduced incidence of COVID-19 among kidney transplant recipients. The lack of reduction in lethality rates is perhaps associated with the low percentage of patients developing humoral response after the second dose.

Comparison of 30-day case-fatality rate between dialysis and transplant Covid-19 patients: a propensity score matched cohort study.

BACKGROUND AND OBJECTIVES: Patients undergoing kidney replacement therapies (KRTs) have a poor prognosis after Covid-19 infection. Few studies have compared the outcomes of such patients in the different KRT modalities. This study aimed to analyze the 30-day Covid-19-associated case-fatality rate of dialysis and kidney transplant patients. METHODS: Retrospective cohort study analyzing data from patients with confirmed Covid-19 between Mar/20 and Jan/21 included in two multicenter studies, the Brazilian Covid-19 Dialysis Study (Dialysis group, n = 703) and the Covid-19-KT Brazilian Study (Transplant group, n = 1907). To assess the risk factors for death, adjusted Cox hazards models were used. A sensitivity analysis was performed using a propensity score analysis to match the groups (n = 587 patients in each group). RESULTS: A higher percentage of transplant patients required hospitalization (68 vs. 51%, p < 0.001), intensive care (37 vs. 30%, p = 0.023), and invasive mechanical ventilation (28 vs. 22%, p = 0.035). Multivariate analysis of the before-matching sample showed that subjects in the transplant group were at a lower death risk at baseline (HR 0.380.560.85). However, they showed higher risk over time (HR 1.031.061.09). Kaplan-Meier analysis after propensity score matching confirmed the inferior 30-day cumulative survival in the transplant recipients (83 vs. 78%, p = 0.0014). CONCLUSION: Both transplant and dialysis patients have high 30-day case-fatality rates after a Covid-19 diagnosis. Despite lower death risk at baseline, transplant patients have an increased death risk of 6% per day than dialysis patients.

Comparison of 30-day case-fatality rate between dialysis and transplant Covid-19 patients: a propensity score matched cohort study

Background and objectives Patients undergoing kidney replacement therapies (KRTs) have a poor prognosis after Covid-19 infection. Few studies have compared the outcomes of such patients in the different KRT modalities. This study aimed to analyze the 30-day Covid-19-associated case-fatality rate of dialysis and kidney transplant patients. Methods Retrospective cohort study analyzing data from patients with confirmed Covid-19 between Mar/20 and Jan/21 included in two multicenter studies, the Brazilian Covid-19 Dialysis Study (Dialysis group, n = 703) and the Covid-19-KT Brazilian Study (Transplant group, n = 1907). To assess the risk factors for death, adjusted Cox hazards models were used. A sensitivity analysis was performed using a propensity score analysis to match the groups (n = 587 patients in each group). Results A higher percentage of transplant patients required hospitalization (68 vs. 51%, p < 0.001), intensive care (37 vs. 30%, p = 0.023), and invasive mechanical ventilation (28 vs. 22%, p = 0.035). Multivariate analysis of the before-matching sample showed that subjects in the transplant group were at a lower death risk at baseline (HR 0.380.560.85). However, they showed higher risk over time (HR 1.031.061.09). Kaplan–Meier analysis after propensity score matching confirmed the inferior 30-day cumulative survival in the transplant recipients (83 vs. 78%, p = 0.0014). Conclusion Both transplant and dialysis patients have high 30-day case-fatality rates after a Covid-19 diagnosis. Despite lower death risk at baseline, transplant patients have an increased death risk of 6% per day than dialysis patients. Graphical Abstract Supplementary Information The online version contains supplementary material available at 10.1007/s40620-021-01172-1.