Evolving impact of the COVID-19 pandemic in chronic dialysis recipients over the course of pandemic waves and COVID-19 vaccination rollout: a French national study. (preprint)

BackgroundThis observational study aims to assess the impact of the pandemic on the evolving of kidney transplantations, survival, and vaccination in chronic dialysis recipients (CDR) over the COVID-19 pandemic subperiods. MethodsUsing the French national health claims database, incident persons with end stage kidney disease in years 2015 to 2021 treated with dialysis were followed-up until December 31, 2022. Kidney transplantion and survival over pandemic subperiods versus the prepandemic period were investigated using longitudinal models with time-dependent covariates. Moreover, the impact of cumulative doses of COVID-19 vaccine on hospitalization and survival were compared between CDR and matched-control individuals. FindingsFollow-up of the 71,583 CDR and 143,166 controls totalized 639,341 person-years (CDR: 184,909; controls: 454,432). The likelihood of receiving a kidney transplant decreased during all pandemic subperiods except one. Mortality in CDR increased during the 3 wave subperiods (hazard ratio (HR [95% confidence interval]): 1{middle dot}19 [1{middle dot}13-1{middle dot}27], 1{middle dot}19 [1{middle dot}15-1{middle dot}23], and 1{middle dot}12 [1{middle dot}07-1{middle dot}17], respectively). While vaccine coverage declined with each booster dose, receiving such doses was associated with lower risks of COVID-19-related hospitalization (0{middle dot}66 [0{middle dot}56-0{middle dot}77], 0{middle dot}83 [0{middle dot}72-0{middle dot}94] for 1st booster versus 2nd dose and 2nd booster versus 1st booster, respectively) and death (corresponding HR: 0{middle dot}55 [0{middle dot}51-0{middle dot}59], 0{middle dot}88 [0{middle dot}83-0{middle dot}95]). Evolving patterns in mortality and vaccination outcomes were similar in CDR and controls. InterpretationThe impact of the pandemic in CDR was not specific of the kidney disease per se. Study results also suggest future research aimed at increasing adherence to vaccine booster doses.

Expected and observed deaths in France from 2020 to 2022: accurately assessing the excess mortality during the COVID-19 pandemic period. (preprint)

Background: Excess mortality has been used worldwide for summarizing the COVID-19 pandemic-related burden. In France, the reported estimates for years 2020 and 2021 vary by a factor of three, and reported evolving trends for year 2022 are discordant. Objectives: We aimed at selecting the most appropriate modelling approach enabling an accurate estimation of the excess mortality in France during the 2020-2022 pandemic years. Method: Based on the 18,646,089 deaths that occurred In France between 1990 and 2023, the natural trend of age-and gender-specific death rates over time was considered according to three models which performances were compared for accurately predicting mortality data in the absence of pandemic perturbations. The best modelling approach was then used for estimating age-and gender-specific excess deaths and corresponding expected years of life lost in the individuals deceased in 2020, 2021, and 2022. Results: A quadratic model trained with years 2010-2019 estimated that 49,352 [40,257; 58,165] (mean [95% confidence interval]), 43,028 [29,071; 56,381], and 54,373 [34,696; 73,187] excess deaths occurred in France in 2020, 2021 and 2022, respectively. Corresponding years of life lost rose over time with 503,289 [446,347; 561,415], 581,495 [493,911; 671,162], and 667 439 [544,196; 794,225] years of life lost for the individuals deceased in 2020, 2021, and 2022, respectively. Conclusion: The study proposes a reliable method for accurately estimating excess mortality. Applying this method to the 2020-2022 years of the COVID-19 pandemic in France yielded estimates of excess mortality that peaked in year 2022.

Direct and indirect impact of the COVID-19 pandemic on the survival of kidney transplant recipients: a national observational study in France. (preprint)

Background During the pandemic period, healthcare systems were substantially reorganized for managing COVID-19 cases. The corresponding changes on the standard care of persons with chronic diseases and the potential consequences on their outcomes remain insufficiently documented. This observational study investigates the direct and indirect impact of the pandemic period on the survival of kidney transplant recipients (KTR), in particular in those not hospitalized for COVID-19. Methods We conducted a cohort study using the French national health data system which contains all healthcare consumptions in France. Incident persons with end stage kidney disease between January 1, 2015 and December 31, 2020 who received a kidney transplant were included and followed-up from their transplantation date to December 31, 2021. The survival of KTR during the pre-pandemic and pandemic periods was investigated using Cox models with time-dependent covariates, including vaccination and hospitalization events. Findings There were 10,637 KTR included in the study, with 324 and 430 deaths observed during the pre-pandemic (15,115 person-years of follow-up) and pandemic periods (14,657 person-years of follow-up), including 127 deaths observed among the 659 persons with a COVID-19-related hospitalization. In multivariable analyses, the risk of death during the pandemic period was similar to that observed during the pre-pandemic period (hazard ratio (HR) [95% confidence interval]: 0.92 [0.77-1.11]), while COVID-19-related hospitalization was associated with an increased risk of death (HR: 10.62 [8.46-13.33]). In addition, pre-emptive kidney transplantation was associated with a lower risk of death (HR: 0.71 [0.56-0.89]), as well as a third vaccine dose (HR: 0.42 [0.30-0.57]), while age, diabetes and cardiovascular diseases were associated with higher risks of death. Interpretation Considering persons living with a kidney transplant with no severe COVID-19-related hospitalization, the pandemic period was not associated with a higher risk of death.

Hospital admissions and mortality for acute exacerbations of COPD during the COVID-19 pandemic: a nationwide study in France (preprint)

Background: A global reduction in hospital admissions for acute exacerbations of chronic obstructive pulmonary disease (AECOPD) was observed during the first months of the COVID-19 pandemic. Large-scale studies covering the entire pandemic period are lacking. We investigated hospitalizations for AECOPD and the associated in-hospital mortality at the national level in France during the first two years of the pandemic. Methods: We used the French National Hospital Database to analyse the time trends in (1) monthly incidences of hospitalizations for AECOPD, considering intensive care unit (ICU) admission and COVID-19 diagnoses, and (2) the related in-hospital mortality, from January 2016 to November 2021. Pandemic years were compared with the pre-pandemic years using Poisson regressions. Results: The database included 565,890 hospitalizations for AECOPD during the study period. The median age at admission was 74 years (interquartile range 65-83), and 37% of the stays concerned women. We found: (1) a dramatic and sustainable decline in hospitalizations for AECOPD over the pandemic period (from 8,899 to 6,032 monthly admissions, relative risk (RR) 0.65, 95% confidence interval (CI) 0.65-0.66), and (2) a concomitant increase in in-hospital mortality for AECOPD stays (from 6.2% to 7.6% per month, RR 1.24, 95% CI 1.21-1.27). The proportion of stays yielding ICU admission was similar in the pre-pandemic and pandemic years, 21.5% and 21.3%, respectively. In-hospital mortality increased to a greater extent for stays without ICU admission (RR 1.39, 95% CI 1.35-1.43) than for those with ICU admission (RR 1.09, 95% CI 1.05-1.13). Since January 2020, only 1.5% of stays were associated with a diagnosis of COVID-19, and their mortality rate was nearly 3-times higher than those without COVID-19 (RR 2.66, 95% CI 2.41-2.93). Conclusion: The decline in admissions for AECOPD during the pandemic could be attributed to a decrease in the incidence of exacerbations for COPD patients and/or to a possible shift from hospital to community care. The rise in in-hospital mortality is partially explained by COVID-19, and could be related to restricted access to ICUs for some patients and/or to greater proportions of severe cases among the patients hospitalized during the pandemic.

Biased and unbiased estimation of the average lengths of stay in intensive care units in the COVID-19 pandemic (preprint)

Background: The average length of stay (LOS) in the intensive care unit (ICU_ALOS) is a helpful parameter summarizing critical bed occupancy. During the outbreak of a novel virus, estimating early a reliable ICU_ALOS estimate of infected patients is critical to accurately parameterize models examining mitigation and preparedness scenarios. Methods: Two estimation methods of ICU ALOS were compared: the average LOS of already discharged patients at the date of estimation (DPE), and a standard parametric method used for analyzing time-to-event data which fits a given distribution to observed data and includes the censored stays of patients still treated in the ICU at the date of estimation (CPE). Methods were compared on a series of all COVID-19 consecutive cases (n=59) admitted in an ICU devoted to such patients. At the last follow-up date, 99 days after the first admission, all patients but one had been discharged. A simulation study investigated the generalizability of the methods' patterns. CPE and DPE estimates were also compared to COVID-19 estimates reported to date. Findings: LOS [≥] 30 days concerned 14 out of the 59 patients (24%), including 8 of the 21 deaths observed. Two months after the first admission, 38 (64%) patients had been discharged, with corresponding DPE and CPE estimates of ICU_ALOS (95%CI) at 13.0 days (10.4, 15.6) and 23.1 days (18.1, 29.7), respectively. Series' true ICU_ALOS was greater than 21 days, well above reported estimates to date. Interpretation: Discharges of short stays are more likely observed earlier during the course of an outbreak. Cautious unbiased ICU_ALOS estimates suggest parameterizing a higher burden of ICU bed occupancy than that adopted to date in COVID-19 forecasting models. Funding: Support by the National Natural Science Foundation of China (81900097 to Dr. Zhou) and the Emergency Response Project of Hubei Science and Technology Department (2020FCA023 to Pr. Zhao).