ABSTRACT
Global infections are very frequent cause of AKI. Often this is due to the non-specific systemic effects of sepsis and volume depletion and therefore can occur with many infectious agents perhaps most searingly brought to our attention with the SARS-CoV-2 pandemic. The kidney can also be damaged by infections directly involving the renal parenchyma, because of persistent infection elsewhere in the body, as a post-infectious response and secondary diseases causing obstruction. Identifying, first, that kidney injury is due to infection and the particular infection causing the patient's presentation is critical to management. Some infections discussed in this chapter are confined to specific areas of the world, but with increasing global travel and migration, patients may present to healthcare facilities anywhere;thus, a thorough travel history is invaluable. © Springer Nature Switzerland AG 2014, 2022.
ABSTRACT
Background: In coronavirus disease 2019 (COVID-19) the need for intervention increases with disease severity and a risk prediction model that incorporates biomarkers would be beneficial for identifying patients for treatment escalation. Aim(s): To investigate biomarkers changes associated with disease severity and outcomes (mortality, thrombosis). Method(s): COVID-19 patients were sampled between April 15 and May 31 2020. Disease severity was assessed by World Health Organization (WHO) ordinal scale. 132 systemic biomarkers were investigated by routine and multiplex assays and statistical analysis performed to characterise the biomarker profile of COVID-19 patients associated with disease severity, duration, survival and thrombosis. Result(s): The study enrolled 150 COVID-19 positive adults and 16 healthy volunteers. The average age was 64 years, 59% were male, 85% had co-morbidities, 33% had a thrombotic event, and 13% died. A cross comparative analysis of biomarkers identified 13 biomarkers common to severity, mortality and thrombosis with significant correlation;including endothelial dysfunction (VWF, tPA, TFPI), hypercatabolism (low albumin, Hb, FXIII) and inflammatory response (IL-8, Osteopontin). Similarly, 14 biomarkers associated with severity and mortality included pro-inflammatory cytokines and their receptors (sTNFRII, STNFRI, sIL2a, IL6, MIP1a), neutrophils (elevated WBC, Neutrophils, TIMP1) and tissue remodelling (SCGF, EG3A). Nine biomarkers common across severity and thrombosis were angiogenesis (VEGF, LYVE1, Follistatin), acute phase response (SAP, AGP) and clot formation (Fibrinogen and PAPs). Conclusion(s): The biomarker profile associated with poorer outcomes indicates an inflammatory response, endothelial cell disruption, hypercoagulability and hypercatabolism. This study has identified several biomarkers that may be useful indicators of disease severity and progression. Further work is needed to determine how these may be used to direct clinical management. (Figure Presented).
ABSTRACT
Background: Alveolar fibrin deposition and pulmonary microthrombi are pathophysiological features of COVID-19- induced respiratory failure. Nebulised thrombolysis offers locally targeted therapy with potentially lower bleed risk than systemic administration. Aim(s): To investigate the safety and potential for clinical efficacy of nebulised recombinant tissue plasminogen activator (rt-PA) for improving oxygenation in patients hospitalised with COVID-19 complicated by mild to severe acute respiratory distress syndrome (ARDS). Method(s): Patients hospitalised with severe COVID-19 and a PaO2/ FiO2 (P/F) ratio of <300 (units), requiring invasive mechanical ventilation (IMV) or non-invasive respiratory support (NIRS) received 40-60 mg per day of rt-PA, dosed for <=14 days in a phase II, open-label, single-centre pilot study. Efficacy was assessed via improved oxygenation. Safety was assessed by treatment-related serious adverse event bleeding and reduction of fibrinogen to <1.0-1.5 g/L. Result(s): Nine (Cohort 1 [C1];6/9 IMV, 3/9 NIRS) and 26 adults (Cohort 2 [C2];12/26 IMV, 14/26 NIRS) received nebulised rt-PA alongside standard of care. Matched historical controls (HC) (n = 18) were used for comparison in C1. Mean P/F ratio increased in both C1 groups from baseline (BL) to end of study (EOS) (rt-PA;154.4 to 298.8 vs. HC;154.1 to 211.6);a linear mixed effect model confirmed higher P/F ratios in the rt-PA group. Among C2 groups, greater improvements in mean P/F ratio from BL to EOS were seen in the NIRS group (NIRS;125.5 to 239.4 vs. IMV;120.3 to 188.2). Four potentially treatment-related bleeds were reported;no clinically significant fibrinogen reductions were observed. Lower mortality was observed in the C1 rt-PA group (11.1%) vs. the HC group (55.6%) and in the C2 NIRS group (21.4%) vs. the IMV group (41.7%). Conclusion(s): Nebulised rt-PA is well-tolerated, improves oxygenation in patients with COVID-19- related ARDS, and merits a randomised controlled trial to confirm efficacy and potentially identify a subgroup of interest.
ABSTRACT
This case study will focus on clinical presentation and evidence-based management of patients with severe COVID-19. Risk factors for mortality and predictors of severity will be discussed. In addition to best standard of care, we will explore evolving data on the use of antiviral and immune-modulatory therapy.