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.

No evidence of clinical efficacy of hydroxychloroquine in patients hospitalized for COVID-19 infection with oxygen requirement: results of a study using routinely collected data to emulate a target trial (preprint)

Background Treatments are urgently needed to prevent respiratory failure and deaths from coronavirus disease 2019 (COVID-19). Hydroxychloroquine (HCQ) has received worldwide attention because of positive results from small studies. Methods We used data collected from routine care of all adults in 4 French hospitals with documented SARS-CoV-2 pneumonia and requiring oxygen [≥] 2 L/min to emulate a target trial aimed at assessing the effectiveness of HCQ at 600 mg/day. The composite primary endpoint was transfer to intensive care unit (ICU) within 7 days from inclusion and/or death from any cause. Analyses were adjusted for confounding factors by inverse probability of treatment weighting. Results This study included 181 patients with SARS-CoV-2 pneumonia; 84 received HCQ within 48 hours of admission (HCQ group) and 97 did not (no-HCQ group). Initial severity was well balanced between the groups. In the weighted analysis, 20.2% patients in the HCQ group were transferred to the ICU or died within 7 days vs 22.1% in the no-HCQ group (16 vs 21 events, relative risk [RR] 0.91, 95% CI 0.47-1.80). In the HCQ group, 2.8% of the patients died within 7 days vs 4.6% in the no-HCQ group (3 vs 4 events, RR 0.61, 95% CI 0.13-2.89), and 27.4% and 24.1%, respectively, developed acute respiratory distress syndrome within 7 days (24 vs 23 events, RR 1.14, 95% CI 0.65-2.00). Eight patients receiving HCQ (9.5%) experienced electrocardiogram modifications requiring HCQ discontinuation. Interpretation These results do not support the use of HCQ in patients hospitalised for documented SARS-CoV-2-positive hypoxic pneumonia.