ABSTRACT
Background. Solid organ transplant (SOT) recipients are at higher risk than general population for complicated COVID-19 course. Moreover COVID-19 vaccination in this setting is associated with a suboptimal immune response. However, the impact of this finding on the risk of breakthrough infection (BI) in SOT recipients has to be yet determined. Methods. Single-center prospective longitudinal cohort of adult SOT recipients who received three doses of mRNA COVID-19 vaccine between February and December 2021 and were followed up to March 30 2022. Patients were tested for antibody response at several timepoints (1 st dose, 2 nd dose, 3+/-1 month after 1 st dose, and 1 month after 3 rd dose). Main endpoints were: i) BI defined as laboratory confirmed SARS-CoV2 infection diagnosed >=14 day after 2 nd dose;ii) positive antibody response (AbR) defined as anti-rapid binding domain titer >=5 U/ml determined by Elecsys Anti-SARS-CoV-2 ECLIA assay (Roche Diagnostics, CH), the last available determination before BI was considered. Results. Study cohort consists of 642 SOT (277 kidney, 191 liver, 144 heart, 37 lung) recipients: 63.9% males, median age 54 +/- 14.5 years. Of them, 111 (17.8%) developed BI, BI rates were 19.9%, 18.1%, 15.2% and 10.8% among liver, heart, kidney and lung transplant recipients, respectively. Positive-AbR was observed in 60% of all patients, but rates varied from 8.7% to 91.3% among patients with BI and without BI, respectively. Predictors of BI infection at multivariable analysis were liver (vs. other grafts) transplant (OR 2.98, 95%CI 1.47-6.03), mycophenolate (1.63, 0.92-2.88) and steroids (1.8, 1.05- 3.33), while positive-AbR (0.61, 0.35-1.04) and age (0.97, 0.95-0.99) were protective. On the other hand, liver transplant (1.94, 1.02-3.69), time from transplant (1.09, 1.05-1.21), and Moderna vaccine (2.32, 1.46-3.70) were associated with positive-AbR, while age (0.97, 0.95-0.98), heart transplant (0.56, 0.33-0.96), mycophenolate (0.65, 0.39-1.06) and steroids (0.39, 0.23-0.65) with lower probability of positive-AbR. Conclusion. Although associated with positive-AbR, liver transplant and younger age were also BI predictors, suggesting the importance of social factors and the controversial role of immune monitoring.
ABSTRACT
BACKGROUND AND AIMS: Many studies are available that reported a higher risk of COVID-19 disease among patients on dialysis or with kidney transplantation, and the poor outcome of COVID-19 in these patients. Patients in conservative therapy for chronic kidney disease (CKD) have received lower attention, therefore little is known about how COVID-19 may affect this population. The aim of this study was to analyse the COVID-19 incidence and mortality in CKD patients followed up in an integrated healthcare program, living in a small area of Northern Italy. METHOD: The study population included CKD patients from the Emilia-Romagna Prevention of Progressive Renal Insufficiency (PIRP) project, followed up in the 4 nephrology units (Ravenna, Forlì, Cesena and Rimini) of AUSL Romagna (Italy) and alive at 1.01.2020. All patients were in conservative therapy and none of them had initiated dialysis or received kidney transplantation. The hospital discharge database was used to identify patients hospitalized with COVID-19 up to 31.07.2020, and the mortality database was used to assess mortality among patients with COVID-19 at the same date. Multivariable logistic regression was used to identify predictors of COVID- 19 disease, and Kaplan-Meier survival analysis to identify predictors of COVID-19 mortality. Excess mortality of 2020 compared to mortality in 2015-19 in the PIRP cohort was also estimated. RESULTS: COVID-19 incidence among CKD patients was 4.09% (193/4716 patients), while in the general population it was 0.46% (5,195/1,125,574). COVID-19 was more likely in CKD patients with older age (Odds Ratio=1.038), cardiovascular comorbidities (OR=2.217), COPD (OR=1.559) and less likely in patients living in the province of Ravenna (OR=0.468), that was hit later by the first wave of pandemic compared to the other areas of AUSL Romagna. Baseline eGFR was lower in CKD patients with COVID-19 (31.7 vs. 35.8 ml/min/1.73 m2), but this difference did not reach statistical significance (p=0.066). As of 31.07.2020, the crude mortality rate among CKD patients with COVID-19 was 44.6% (86/193), compared to 4.7% (215/ 4523) in CKD patients without COVID-19 and to 14.5% (4289/29670) in the general population with COVID-19 of the Emilia-Romagna region. Factors associated with mortality of CKD patients with COVID-19 were older age (p=0.034) and the period of COVID-19 onset (p=0.003). The highest crude mortality rate (71.4%) was found in CKD patients for whom COVID-19 onset occurred between 8 and 21 March. The excess mortality of January-July 2020 with respect to the average mortality of January- July 2015-19 in the PIRP cohort was +17.7%, corresponding to 77 excess deaths. March-April was the period with the highest excess mortality (+69.8%), while in January-February a 15.9% lower mortality was observed with respect to the corresponding months of the five previous years. CONCLUSION: In our study, including a cohort of regularly followed up CKD patients, the risk of COVID-19 disease and of COVID-19 related mortality was comparable, or even somewhat higher, to that observed in patients on dialysis and those who received kidney transplantation. The incidence of COVID-19 in CKD patients was higher in the areas of AUSL Romagna earlier affected by the pandemic wave, whereas mortality rates were similar across all areas. CKD patients represent a population very vulnerable to COVID-19 disease, and their protection should be highly prioritized in the models of care and prevention measures.
ABSTRACT
OBJECTIVES: The objective of the study is to compare excess mortality (EM) patterns and spatial correlation between the first and second wave of the pandemic in Lombardy, the Italian region that paid an extremely high COVID-19-related mortality toll in March and April 2020. STUDY DESIGN: We conducted a longitudinal study using municipality-level mortality data. METHODS: We investigated the patterns and spatial correlation of EM of men aged ≥75 years during the first two pandemic waves (March-April 2020 vs November 2020) of COVID-19, using the mortality data released by the Italian National Institute of Statistics. EM was estimated at the municipality level to accurately detect the critical areas within the region. RESULTS: The areas that were mostly hit during the first wave of COVID-19 were generally spared by the second wave: EM of men aged ≥75 years in the municipality of Bergamo plummeted from +472% in March and April to -13% in November, and in Cremona the variation was from +344% to -19%. Conversely, in November 2020 EM was higher in some areas that had been protected in the first wave of the pandemic. Spatial correlation widely corroborates these findings, as large sections of the hot spots of EM detected in the first wave of the pandemic changed into cold spots in the second wave, and vice versa. CONCLUSIONS: Our results reveal the specular distribution of EM between the first and second wave of the pandemic, which may entail the consequences of social distancing measures and individual behaviors, local management strategies, 'harvesting' of the frailer population and, possibly, acquired immune protection. In conclusion, our findings support the need for continuous monitoring and analysis of mortality data using detailed spatial resolution.