Elevated tacrolimus levels among COVID-19 kidney transplant recipients are associated with worse disease severity and clinical outcomes.

BACKGROUND: The therapeutic effects of immunosuppressive drugs against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections causing coronavirus disease 2019 (COVID-19) are being actively investigated. However, COVID-19's potential effects on serum calcineurin inhibitor levels have only been described recently. This study aimed to evaluate COVID-19's effect on tacrolimus levels in renal transplant recipients with moderate to severe symptoms and to assess their potential correlation with disease severity. MATERIALS AND METHODS: We retrospectively investigated 50 kidney transplant recipients with moderate to severe COVID-19. Their tacrolimus trough level on admission was compared to baseline levels, and their laboratory measurements and clinical course were reviewed on days 1 (admission), 7, 14, and 28. RESULTS: We found that 90% of patients had admission tacrolimus trough levels above baseline, with a mean increase of 176%. In addition, 71% had tacrolimus trough levels ≥ 50% above baseline, and 40% had supra-therapeutic trough levels of > 15 ng/mL. Supra-therapeutic trough levels were associated with greater hypoxemic respiratory failure, acute kidney injury, and increased 30-day mortality. CONCLUSION: Elevated tacrolimus levels occur in many renal transplant recipients with moderate to severe COVID-19 and are associated with worse clinical outcomes. Close drug monitoring is crucial to avoid toxicities and minimize over-immunosuppression complications.

Fluvial CO2 and CH4 patterns across wildfire-disturbed ecozones of subarctic Canada: Current status and implications for future change.

Despite occupying a small fraction of the landscape, fluvial networks are disproportionately large emitters of CO2 and CH4 , with the potential to offset terrestrial carbon sinks. Yet the extent of this offset remains uncertain, because current estimates of fluvial emissions often do not integrate beyond individual river reaches and over the entire fluvial network in complex landscapes. Here we studied broad patterns of concentrations and isotopic signatures of CO2 and CH4 in 50 streams in the western boreal biome of Canada, across an area of 250,000 km2 . Our study watersheds differ starkly in their geology (sedimentary and shield), permafrost extent (sporadic to extensive discontinuous) and land cover (large variability in lake and wetland extents). We also investigated the effect of wildfire, as half of our study streams drained watersheds affected by megafires that occurred 3 years prior. Similar to other boreal regions, we found that stream CO2 concentrations were primarily associated with greater terrestrial productivity and warmer climates, and decreased downstream within the fluvial network. No effects of recent wildfire, bedrock geology or land cover composition were found. The isotopic signatures suggested dominance of biogenic CO2 sources, despite dominant carbonate bedrock in parts of the study region. Fluvial CH4 concentrations had a high variability which could not be explained by any landscape factors. Estimated fluvial CO2 emissions were 0.63 (0.09-6.06, 95% CI) and 0.29 (0.17-0.44, 95% CI) g C m-2  year-1 at the landscape scale using a stream network modelling and a mass balance approach, respectively, a small but potentially important component of the landscape C balance. These fluvial CO2 emissions are lower than in other northern regions, likely due to a drier climate. Overall, our study suggests that fluvial CO2 emissions are unlikely to be sensitive to altered fire regimes, but that warming and permafrost thaw will increase emissions significantly.