Changing of therapeutic trends between the 1st and 2nd wave did not reduce COVID-19 related mortality of renal transplant recipients: a national registry study. (preprint)

SARS-CoV-2 pandemic evolved in two consecutive waves over 2020 (for France: 1st wave from March 1 to July 31; and 2nd wave from August 1 to December 31). Improvements in the management of COVID-19 led to a reduction of mortality rates in hospitalized patients during the second wave. Whether this progress also benefited to kidney transplant recipients (KTR), a population particularly vulnerable to severe COVID-19, remained unclear. In France, 957 KTR were hospitalized for COVID-19 in 2020 and their data were prospectively collected in the French SOT COVID registry. The presentation, management, and outcomes of the 359 KTR diagnosed during the 1st wave were compared to those of the 598 of the 2nd wave. Baseline comorbidities were largely similar between KTR of the 2 waves. Maintenance immunosuppression was reduced in most patients but withdrawal of antimetabolite (73.7% vs 58.4%, p<0.001) or CNI (32.1% vs 16.6%, p<0.001) was less frequent during the 2nd wave. Hydroxychloroquine and azithromycin that were commonly used during the 1st wave (21.7% and 30.9%, respectively) were almost abandoned during the 2nd. In contrast, the use of high dose corticosteroids doubled (19.5% vs. 41.6%, p<0.001). Despite these changing trends in COVID-19 management, 60-day mortality was not statistically different between the 2 waves (25.3% vs. 23.9%; Log Rank, p=0.48). We conclude that changing of therapeutic trends during 2020 did not reduce COVID-19 related mortality in KTR. Our data indirectly support the importance of vaccination and monoclonal neutralizing anti-SARS-CoV-2 antibodies to protect KTR from severe COVID-19.

Kinetics of Biomarkers Associated with Organ Dysfunction and Inflammatory Status and Their Association with Disease Outcomes in Severe COVID-19: A Longitudinal Cohort Study (preprint)

BACKGROUND: COVID-19 can induce pulmonary and systemic inflammation and subsequent multi-organ dysfunction. In patients with severe COVID-19, no data are available on the longitudinal evolution of biochemical abnormalities and their ability to predict disease outcomes. METHODS: Using a retrospective, longitudinal cohort study design on consecutive patients with severe COVID-19, we monitored biomarker kinetics to estimate the occurrence of organ dysfunction and the severity of the inflammatory reaction and their association with acute respiratory failure (ARF) and death through multilevel modeling adapted for repeated measures. FINDINGS: A total of 162 patients were assessed and did not receive antiviral therapy against SARS-CoV-2. During the study period, 1151 biochemical explorations were carried out for up to 59 biochemical markers in blood and urine, totaling 15,260 biochemical values. The spectrum of biochemical abnormalities and their kinetics were consistent with a multi-organ involvement, including lung, kidney, heart, liver (major cytolysis, cholestasis, conjugated hyperbilirubinemia), muscle (major cytolysis), and pancreas (hyperlipasemia) along with a severe inflammatory syndrome. On the 20 more representative biochemical markers (>250 iterations), only CRP >90 mg/L (odds ratio [OR] 6·87, 95% CI, 2·36–20·01) and urea nitrogen >0·36 g/L (OR 3·91, 95% CI, 1·15–13·29) were independently associated with the risk of ARF. Urea nitrogen >0·42 g/L was the only marker associated with the risk of COVID-19 related death. The proportion of patients who developed an acute kidney injury (AKI) stage 3, increased significantly during follow-up (0·9%, day 0; 21·4%, day 14; P <0·001). INTERPRETATION: Our results point out the lack of the association between the inflammatory markers and the risk of death but rather highlight a significant association between renal dysfunction and the risk of COVID-19 related acute respiratory failure and death. Further studies should address the significance of acute kidney injury in the prediction of COVID-19 related death. FUNDING: No funding.DECLARATION OF INTERESTS: The authors who have taken part in this study declare that they do not have anything to disclose regarding conflicts of interest concerning this manuscript.ETHICS APPROVAL STATEMENT: The “Nancy Biochemical Database” is registered at the French National Commission on Informatics and Liberty, CNIL, under the record N°1763197v0. The Ethics committee of the University Hospital of Nancy approved the study (ID: 2020/264).