Massive polyuria associated with severe COVID-19-related pneumonia complicated by pulmonary embolism

Coronavirus disease 2019 (COVID-19) predominantly manifests with signs of respiratory system injury;however, multi-systemic manifestations may occur. Renal pathology develops in up to 80% of patients with COVID-19. The aim of the study was to describe the case of isolated massive polyuria of unknown etiology in the patient with severe COVID-19-related pneumonia complicated by pulmonary embolism (PE). A 54-year-old male with bilateral pneumonia, related to COVID-19, developed PE. The next day after successful thrombolysis with alteplase (90 mg) the diuresis of the patient began to increase and fluctuated between 5000 mL and 8000 mL. The diuresis returned to normal ranges two weeks after PE episode. The rise of the diuresis was not accompanied by electrolyte disorders and elevation of serum creatinine. Changes in the urine tests were minimal, only once the urine protein was detected (0.25 g/L). The highest urine excretion was observed in evening hours (16.00-24.00). Chest CT on the day 14 after the patient's admission revealed 90% of lung tissue injury, cranial CT showed no brain abnormalities, including hypothalamus and pituitary gland. The patient's condition met neither diagnostic criteria of acute kidney injury, nor acute interstitial nephritis, nor pituitary gland damage. The course of the polyuria in the presented case was benign (self-limiting, no blood electrolyte abnormalities, compensated by oral rehydration only). Polyuria in patients with COVID-19 may not be a life-threatening condition that does not require active treatment.Copyright © 2021 EDIZIONI MINERVA MEDICA.

Plasminogen activator inhibitor-1 (PAI-1) like the best mortality predictor of in the COVID-19-associated pneumonia

The aim was to estimate the prognostic role of PAI-1 on admission in hospitalized patients with confirmed COVID-19 pneumonia. Material(s) and Method(s): We observed 2 groups: Main - 85 patients (59 (52;65) years, men - 45 (52.9%)), hospitalized with COVID-19 pneumonia;Control - 25 healthy volunteers (50.0 (35;65) years, men - 13 (52.0%)). General tests, PAI-1 (ELISA Kit, Elabscience) before anticoagulants, autopsy data, statistic. Result(s): At admission the level of PAI-1 in Main group was in 60 times higher than in Control group (6.1 [0.15;18] ng/ml versus 0.1 [0.09;0.11] ng/ml, p=0,000). Despite the adequate treatment 12 patients died from COOVID-19 pneumonia. Maximal levels of PAI-1 were in died patients. ROC analysis shows the powerful reliable connection between increased level of PAI-1 higher than 20,6 ng/ml at admission and COVID-19 mortality (OR=219;CI=95% (7,7056 to 6224,1404);p=0,0016). Conclusion(s): 1) problem in fibrinolysis plays the crucial role in thrombogenesis in COVID-19;2) increased PAI-1 more than 20 ng/l is associated with 200-times higher risk of mortality. (Figure Presented).

The role of NT-proBNP in patients discharged after COVID-19 pneumonia

The aim: of study was to define the cardiac disorders in the early post-COVID-19 period. Material(s) and Method(s): 85 patients(pts) (40 (47,1%) men, age - 44,2 (39,3;47,1)) were observed on 48,3 (45,0;56,2) days after the onset of COVID-19. The main group divided into 3 subgroups: 1 - 39 pts after moderate COVID19 pneumonia, 2 - 36 pts after severe COVID-19 pneumonia, 3 - 10 pts after critical COVID-19 pneumonia. All pts before COVID-19 had no anamnestic data of previous cardiovascular disease. For all pts were performed clinical data, SpO2, echocardiography and measured NT-proBNP in serum. Result(s): All pts had normal SpO2(Me 97,5 (96,3;98,8)%) and saved left ventricular ejection fraction (LVEF) (Me 62,3(60,2;74,3)%). Level of LVEF didn't differ significantly between subgroups (p>0,05). Nevertheless the LVEF, the level of NT-proBNP was significantly higher in patients of subgroup 2 and subgroup 3 (tabl.1), whereas concentration of NT-proBNP in subgroup 1 was not differ from norm (125 pg/ml). Note: *-p<0,01 on Mann-Witney. Conclusion(s): 1) pts after severe and critical COVID-19 pneumonia have high risk for cardiac disorders developing in the early post-COVID-19 period;2) the level of NT-proBNP is the independent predictor of cardiac lesion in early post-COVID-19 period, despite ejection function;3) determination of NT-proBNP is an important element to customize the most appropriate therapeutic strategies for pts after severe and critical COVID-19 pneumonia, not just performing echocardiography.

Mortality Predictors in Covid-19 Pneumonia: Results of Large Roc-Analisis

High mortality rate is one of most important problems in COVID-19. But still now there are no sufficient data how to predict high probability of death in COVID-19 patients (pts). Aim(s): to determine the most probable markers of death in COVID-19 pts. Material(s) and Method(s): 181 pts, who were hospitalized with COVID-19 pneumonia (male - 97 (43,6%), age - 56,7+/-1,04 yrs, SpO2 at admission - 91,7+/-0,6%). All pts were divided into two groups: group 1 included 167 pts (male - 70 (41,9+/-3,8%), age - 56,5+/-1,1 yrs, SpO2 at admission - 92,1+/-0,6%) who successfully treated and discharged from hospital;group 2 included 14 pts (male - 8 (57,1+/-3,2%) (p=0,270), age - 59,7+/-3,1 yrs (p=0,332), SpO2 at admission - 87,6+/-2,8% (p=0,009)) who died. Measurements: clinical examination, SpO2, chest CT, laboratory: CRP, D-dimer, ferritin, ST-2, fibrinogen. Result(s): ROC-analysis: increasing of D-dimer on level <436 ng/ml, ST-2 on level <180 ng/ml, ferritin on level <799 ng/ml can really be predictors of mortality in pts with COVID-19 pneumonia and predict prognosis of disease. Levels of CRP, fibrinogen are not significant predictors of mortality in COVID-19 pneumonia (Fig.1). Conclusion(s): 1) best parameters for mortality prediction in hospitalized patients with COVID-19 are D-dimer, ST-2, ferritin;2) increasing of D-dimer on level <436 ng/ml, ST-2 on level <180 ng/ml, ferritin on level <799 ng/ml at admission can reflect very high risk of mortality in COVID-19 pneumonia. (Figure Presented).

CLINICAL PHENOTYPES OF COVID-19 PNEUMONIA: different phases of viral process or really different states?

During COVID-19 pandemic cases of severe COVID-19 demonstrate heterogeneity among group of patients (pts): some pts are severe because of more expressed respiratory failure, other - because of inflammation, another - because of cardiac and thrombotic complications. Does it different phases of viral process or really different states? Aim: to estimate most valuable categories of pts with severe COVID-19 by separating of clinical phenotypes during cluster analysis. Material(s) and Method(s): 97 pts, who were hospitalized with severe COVID-19 pneumonia (male - 43 (44,3%), age - 58,8+/-1,4yrs, SpO2 - 91,1+/-0,7%). Measurements: clinical examination, SpO2, chest CT, laboratory: CBC, Creactive protein (CRP), D-dimer, Creatine Phosphokinase-MB (CPK-MB), Troponin I, ferritin. Result(s): nevertheless that all pts were severe, cluster analysis shown two heterogeneous groups: 1) with lower saturation and higher thromboinflammation, with lower lymphocytes;2) with higher saturation and lower thromboinflammation, with normal lymphocytes (p<0,002 for all) (Fig. 1). Conclusion(s): 1. Expression of respiratory failure in pts with severe COVID-19 is not an isolated parameter;it is connected with severity of thromboinflammation and cardiac lesion. 2. The estimation of CRP, D-dimer, CPK-MB, troponin I, ferritin can be use as predictors of severity in COVID-19 pneumonia, but the first and screening pathogenetical link is lymphopenia. (Figure Presented).

Prediction of reccurent thrombotic events in survivors after COVID-19

Background: There is an increased risk of thrombotic events in patients with COVID-19, while thrombosis in patients who recovered from COVID-19 is less investigated. Aim(s): To investigate thrombotic events in patients who recovered from COVID-19;to establish risk factors for thrombosis development. Method(s): We reviewed 32 patients who recovered from COVID-19 (M/F:13/19, median age: 57 [49-67] years). Group 1 included 16 patients who had had a thrombotic event, whereas 16 patients from group 2 had not. Statistical analysis was performed by non-parametric methods (median (Me), 95% confidence interval (95% CI), Mann-Whitney U test). We used odds ratio and relative risk to measure the association between risk factors and outcome. Result(s): 15 patients from group 1 had pulmonary embolism, 1 patient had ischemic stroke. The median term of thrombotic events was 45 (32-60) days. 2 patients had thrombophilia, 2 were hospitalized when the outcome occurred. 5 patients had BMI 30 or more, 7 did not have any risk factors. There was no statistically significant difference between two groups regarding age, weight, hospitalization duration, respiratory failure degree and its duration. Comorbidity, hospitalization requirement or oxigenotherapy during COVID-19 did not affect the outcome. The only one association found was increased risk of thrombosis in patients who had not received anticoagulation RR 2.829 (95% CI 1279;6255);OR 9.533 (95% CI 1.847;49.206). Risk was also significantly elevated in case of antiplatelet agent use RR -2.250 (95% CI 0.898;5.636);OR -4.333 (95% CI 0.742;25.295). Conclusion(s): Anticoagulant therapy was the only intervention decreased thrombosis probability in survivors after COVID-19. Absence of anticoagulation treatment increases the risk of thrombosis during post-covid period in 9 times.

The key role of plasminogen activator inhibitor-1 (PAI-1) in the thrombogenesis difference in COVID-19- associated pneumonia compared to bacterial pneumonia

Background: PAI-1 plays a key role in a wide range of physiological and pathological processes, including coagulation, fibrinolysis, inflammation. Aim(s): The aim was to estimate the diagnostic role of PAI-1 on admission in hospitalized patients with COVID-19 pneumonia, comparing with bacterial pneumonia. Method(s): We observed 3 groups: Main (1) -85 patients (mean age -59 (52;65) years, men -45 (52.9%)), hospitalized with pneumonia on the background of laboratory-confirmed (PCR) COVID-19, divided into 3 subgroups: Subgroup 1 -40 patients with moderate COVID-19, subgroup 2 -25 patients with severe COVID-19, subgroup 3 -20 patients with critical COVID-19;Comparative (2) -55 patients (mean age -48.9 (34;62) years, men -30 (54.5%)), hospitalized with community-acquired pneumonia of bacterial etiology (CABP) without COVID-19;Control (3) -25 healthy volunteers (average age -50.0 (35;65) years, men -13 (52.0%)). General analysis, plasma level of PAI-1 (Human PAI-1 ELISA Kit, Elabscience) performed at admission before starting of anticoagulant treatment, statistical analysis. Result(s): At admission the highest level of PAI-1 (6.1 [0.15;18] ng/ ml) was in COVID-19 patients (Main group) and exceeds the Control group (0.1 [0.09;0.11] ng/ml), p1-3 = 0.000) in more than 60 times. Whereas the level of PAI-1 in patients with CABP didn't differ from Control group (0.1 [0.09;0.11] ng/ml), p2-3 = 0.29) (Figure 1).Among COVID-19 group the levels of PAI-1 correlated with the disease severity (Figure 2). Conclusion(s): 1) significantly increase of plasma levels of PAI-1 in COVID-19 pneumonia demonstrates the cornerstone in thrombogenesis of this disease -problems in fibrinolysis system, which is the main difference between CABP;2) in hospitalized patients with COVID-19 pneumonia the level of PAI-1 is associated with the disease severity and could be the crucial marker for patients' distribution. (Figure Presented).

The predictive role of plasminogen activator inhibitor-1 (PAI-1) in the COVID-19- associated pneumonia

Background: PAI-1 plays a key role in a wide range of physiological and pathological processes, including coagulation, fibrinolysis, inflammation. Aim(s): The aim was to estimate the prognostic role of PAI-1 on admission in hospitalized patients with confirmed COVID-19 pneumonia. Method(s): We observed 2 groups: Main -85 patients (age -59 (52;65) years, men -45 (52.9%)), hospitalized with pneumonia on the background of laboratory-confirmed (PCR) COVID-19;Control -25 healthy volunteers (age -50.0 (35;65) years, men -13 (52.0%)). General analysis, determination of PAI-1 (Human PAI-1 ELISA Kit, Elabscience) performed at admission before starting of anticoagulant treatment, autopsy data, statistical analysis. Result(s): At admission the level of PAI-1 in Main group was in 60 times higher than in Control group (6.1 [0.15;18] ng/ml versus 0.1 [0.09;0.11] ng/ml, p=0.000). Despite the adequate treatment 12 patients died from COOVID-19 pneumonia. Maximal levels of PAI-1 were in died patients. ROC analysis shows the powerful reliable connection between increased level of PAI-1 higher than 20.6 ng/ml at admission and COVID-19 mortality (Fig.1) (OR = 219;CI = 95% (7.7056 to 6224.1404);p = 0.0016). Autopsy shown a lot of fibrin clots in lung vessels, which proves the theory that problem in fibrinolysis plays the crucial role in thrombogenesis in COVID-19. Fig.2 demonstrates histological section of the artery of medium caliber, branching of the pulmonary artery, in horizontal projection, a fragment of vascular endothelial integrity violation was isolated, the arrow indicates a pale pink non-nuclear mass in the form of threads -fibrin clot. Conclusion(s): 1) problem in fibrinolysis plays the crucial role in thrombogenesis in COVID-19;2) increased level of PAI-1 at admission more than 20 ng/l is associated with 200-times higher risk of mortality. (Figure Presented).

Community-aquired pneumonia associated with coronavirus disease (COVID-19): determination of pathological process progression predictors by clinical and hemocoagulation parameters

The search for clinical and laboratory markers of COVID-19-associated CAP progression is an urgent problem of today. The aim of our study was to determine the risk factors for the burden of the pathological process by establishing the diagnostic and prognostic significance of clinical and hemocoagulation parameters in the hospital stage of management of patients with CAP on the background of coronavirus disease (COVID-19). The study included 53 individuals of the main group. All patients were examined twice: on the first day of hospitalization (visit 1) and in the dynamics (7-10 days after hospitalization (visit 2)). In 30 (83.3%) patients of subgroup 1, despite adequate treatment, there was an increase in breathing rate and a decrease in saturation to severe (less than 92%) or critical (less than 85%) levels (in 28 and 2 cases respectively). In subgroup 2, the progression of respiratory failure to a critical level was observed in 5 of 12 (41.7%) patients. Conclusions: at the stage of hospitalization of patients with COVID-19-associated CAP the most sensitive clinical predictor of aggravation of the patient's condition is tachypnea of 20 or more;laboratory - the level of D-dimer 200 ng/ml, which increases the risk of progression of the pathological process by 16 times.