Plasma expansion and renal perfusion in critical COVID-19 with AKI

Introduction: We have previously described decreased renal perfusion in acute kidney injury (AKI) due to critical COVID-19 [1]. The objective of this study was to compare the effects of plasma expansion with a standardized fluid bolus on renal perfusion in patients with AKI compared to similar patients without AKI. Method(s): A case control study design was used to investigate group differences before and after a standardized intervention. ICU-treated COVID-19 patients without underlying kidney disease were assigned to two groups based on KDIGO Creatinine criteria for AKI. Renal perfusion was assessed by magnetic resonance imaging using phase contrast and arterial spin labeling before and directly after plasma expansion with 7.5 ml/kg Ringer's Acetate (Baxter). Mean arterial pressure (MAP) was recorded before plasma infusion and compared with maximum value after. Data was analyzed with a mixed model repeated measures ANOVA for all kidneys using a random effect to account for research subjects. Result(s): Nine patients with AKI and eight without were included in the study. Patients in both groups were of similar mean age and weight, 66 (SD 8) years and 94 (SD 22) kg in AKI group and 64 (SD 15) years and 93 (SD 20) kg in patients without AKI. The response to plasma expansion was similar with increased MAP by 18 (CI 8-28) mmHg and 20 (CI 10-31) mmHg respectively (Table 1). Total renal perfusion and cortical perfusion was not significantly changed by plasma expansion, however there was a reduction of medullary perfusion in patients without AKI (Table 1). Conclusion(s): Plasma expansion with a standardized fluid bolus did not increase renal perfusion in critically ill patients with ARDS due to COVID-19.

Increased cerebral blood flow and neuroinflammation post COVID-19

Aim/Introduction: Persisting cerebral symptoms such as fatigue and cognitive dysfunction after Sars-CoV-2 infection are typical for post COVID-19. Positron emission tomography (PET) can contribute to the understanding of post COVID-19 related brain disorders. The aim of this study was to investigate cerebral blood flow (CBF) and neuroinflammation with PET in post COVID-19 patients. Material(s) and Method(s): Data from eight healthy controls (HC) and four subjects with post COVID-19 symptoms were included. At the time of the PET investigation, three subjects had remaining post COVID-19 symptoms, of which one had severe headache. All subjects underwent a 6 min dynamic 15O-water PET scan to measure CBF and a 60 min dynamic 11CPK11195 PET scan to measure neuroinflammation. In addition, all subjects received a T1weighted MRI that was co-registered to the PET images. Parametric images, showing 15O-water CBF and 11CPK11195 binding potential (BPND) at the voxel level, were calculated. Mean total grey matter CBF and BPND values were calculated for all subjects. The co-registered MRI images were normalized to MNI standard space using statistical parametric mapping (SPM12) and the transformation matrices were applied to the respective parametric images. A voxel-wise z-test was performed in SPM12 to compare each 15Owater CBF and 11CPK11195 BPND image from the post COVID-19 patients to the HC CBF and BPND images, respectively. A statistical threshold of p<0.05 was applied. Result(s): Two of the subjects with remaining post COVID-19 symptoms demonstrated a significantly increased CBF in the whole brain compared to the HC. Total grey matter CBF values were 1.27 and 1.41 mL/cm3/min in these two subjects, compared to a mean +/- SD of 0.65 +/- 0.19 mL/cm3/min in the HC group. The subject with persisting headache also showed large clusters of significant increased 11C-PK11195 BPND in the meninges. Mean total grey matter 11CPK11195 BPND values in post COVID-19 subjects were within the range of values in the HC group. The other two subjects did not show increased CBF and no significant increase of 11C-PK11195 BPND. Conclusion(s): Neurological symptoms from post COVID-19 may be due to increased CBF and inflammation. However, further investigations are needed with larger study cohort to better understand the relation between post COVID-19 symptoms and neurological dysfunctions investigated with PET.

Increased cerebral blood flow and neuroinflammation post COVID-19

Aim/Introduction: Persisting cerebral symptoms such as fatigue and cognitive dysfunction after Sars-CoV-2 infection are typical for post COVID-19. Positron emission tomography (PET) can contribute to the understanding of post COVID-19 related brain disorders. The aim of this study was to investigate cerebral blood flow (CBF) and neuroinflammation with PET in post COVID-19 patients. Material(s) and Method(s): Data from eight healthy controls (HC) and four subjects with post COVID-19 symptoms were included. At the time of the PET investigation, three subjects had remaining post COVID-19 symptoms, of which one had severe headache. All subjects underwent a 6 min dynamic 15O-water PET scan to measure CBF and a 60 min dynamic 11CPK11195 PET scan to measure neuroinflammation. In addition, all subjects received a T1weighted MRI that was co-registered to the PET images. Parametric images, showing 15O-water CBF and 11CPK11195 binding potential (BPND) at the voxel level, were calculated. Mean total grey matter CBF and BPND values were calculated for all subjects. The co-registered MRI images were normalized to MNI standard space using statistical parametric mapping (SPM12) and the transformation matrices were applied to the respective parametric images. A voxel-wise z-test was performed in SPM12 to compare each 15Owater CBF and 11CPK11195 BPND image from the post COVID-19 patients to the HC CBF and BPND images, respectively. A statistical threshold of p<0.05 was applied. Result(s): Two of the subjects with remaining post COVID-19 symptoms demonstrated a significantly increased CBF in the whole brain compared to the HC. Total grey matter CBF values were 1.27 and 1.41 mL/cm3/min in these two subjects, compared to a mean +/- SD of 0.65 +/- 0.19 mL/cm3/min in the HC group. The subject with persisting headache also showed large clusters of significant increased 11C-PK11195 BPND in the meninges. Mean total grey matter 11CPK11195 BPND values in post COVID-19 subjects were within the range of values in the HC group. The other two subjects did not show increased CBF and no significant increase of 11C-PK11195 BPND. Conclusion(s): Neurological symptoms from post COVID-19 may be due to increased CBF and inflammation. However, further investigations are needed with larger study cohort to better understand the relation between post COVID-19 symptoms and neurological dysfunctions investigated with PET.

Urinary cytokines correlate with acute kidney injury in critically ill COVID-19 patients.

BACKGROUND: Acute kidney injury is common in COVID-19 patients admitted to the ICU. Urinary biomarkers are a non-invasive way of assaying renal damage, and so far, urinary cytokines are not fully investigated. The current study aimed to assess urinary cytokine levels in COVID-19 patients. METHODS: Urine was collected from COVID-19 patients (n = 29) in intensive care and compared to a preoperative group of patients (n = 9) with no critical illness. 92 urinary cytokines were analyzed in multiplex using the Olink Target 96 inflammation panel and compared to clinical characteristics, and urinary markers of kidney injury. RESULTS: There were strong correlations between proinflammatory cytokines and between urinary cytokines and urinary kidney injury markers in 29 COVID-19 patients. Several cytokines were correlated to kidney injury, 31 cytokines to AKI stage and 19 cytokines correlated to maximal creatinine. CONCLUSIONS: Urinary inflammatory cytokines from a wide range of immune cell lineages were significantly upregulated during COVID-19 and the upregulation correlated with acute kidney injury as well as urinary markers of kidney tissue damage.

Inadequate prophylactic effect of low-molecular weight heparin in critically ill COVID-19 patients.

PURPOSE: The aim of this study was to investigate potential markers of coagulopathy and the effects of thromboprophylaxis with low-molecular-weight heparin (LMWH) on thromboelastography (TEG) and anti-factor Xa in critically ill COVID-19 patients. MATERIAL AND METHODS: We conducted a prospective study in 31 consecutive adult intensive care unit (ICU) patients. TEG with and without heparinase and anti-factor Xa analysis were performed. Standard thromboprophylaxis was given with dalteparin (75-100 IU/kg subcutaneously). RESULTS: Five patients (16%) had symptomatic thromboembolic events. All patients had a maximum amplitude (MA) > 65 mm and 13 (42%) had MA > 72 mm at some point during ICU stay. Anti-factor Xa activity were below the target range in 23% of the patients and above target range in 46% of patients. There was no significant correlation between dalteparin dose and anti-factor Xa activity. CONCLUSIONS: Patients with COVID-19 have hypercoagulability with high MA on TEG. The effect of LMWH on thromboembolic disease, anti-factor Xa activity and TEG was variable and could not be reliably predicted. This indicates that standard prophylactic doses of LMWH may be insufficient. Monitoring coagulation and the LMWH effect is important in patients with COVID-19 but interpreting the results in relation to risk of thromboembolic disease poses difficulties.