Cytokine Hemoadsorption as Rescue Therapy for Critically Ill Patients With SARS-CoV-2 Pneumonia With Severe Respiratory Failure and Hypercytokinemia

Introduction: A dysregulated inflammatory response, known as “cytokine storm”, plays an important role in the pathophysiology of coronavirus 2019 disease (COVID-19). Identifying patients with a dysregulated inflammatory response and at high risk for severe respiratory failure, organ dysfunction, and death is clinically relevant, as they could benefit from the specific therapies, such as cytokine removal by hemoadsorption. This study aimed to evaluate cytokine hemoadsorption as rescue therapy in critically ill patients with SARS-CoV-2 pneumonia, severe respiratory failure refractory to prone positioning, and hypercytokinemia.Methods: In this single center, observational and retrospective study, critically ill patients with SARS-CoV-2 pneumonia, severe acute respiratory failure, and hypercytokinemia were analyzed. All the patients underwent cytokine hemoadsorption using CytoSorb® (Cytosorbents Europe, Berlin, Germany). The indication for treatment was acute respiratory failure, inadequate clinical response to the prone position, and hypercytokinemia.Results: Among a total of 343 patients who were admitted to the intensive care unit (ICU) due to SARS-CoV-2 infection between March 3, 2020 and June 22, 2020, six patients received rescue therapy with cytokine hemoadsorption. All the patients needed invasive mechanical ventilation and prone positioning. A significant difference was found in the pre- and post-treatment D-dimer (17,868 mcg/ml [4,196–45,287] vs. 4,488 mcg/ml [3,166–17,076], p = 0.046), C-reactive protein (12.9 mg/dl [10.6] vs. 3.5 mg/dl [2.8], p = 0.028), ferritin (1,539 mcg/L [764–27,414] vs. 1,197 ng/ml [524–3,857], p = 0.04) and interleukin-6 (17,367 pg/ml [4,539–22,532] vs. 2,403 pg/ml [917–3,724], p = 0.043) levels. No significant differences in the pre- and post-treatment interleukin-10 levels (22.3 pg/ml [19.2–191] vs. 5.6 pg/ml [5.2–36.6], p = 0.068) were observed. Improvements in oxygenation (prehemoadsorption PaO2/FIO2 ratio 103 [18.4] vs. posthemoadsorption PaO2/FIO2 ratio 222 [20.9], p = 0.029) and in the organ dysfunction (prehemoadsorption SOFA score 9 [4.75] vs. posthemoadsorption SOFA score 7.7 [5.4], p = 0.046) were observed. ICU and in-hospital mortality was 33.7%.Conclusions: In this case series, critically ill patients with COVID-19 with severe acute respiratory failure refractory to prone positioning and hypercytokinemia who received adjuvant treatment with cytokine hemoadsorption showed a significant reduction in IL-6 plasma levels and other inflammatory biomarkers. Improvements in oxygenation and SOFA score were also observed.

Severe pulmonary co-infection with varicella-zoster virus, Pneumocystis jirovecii and Cytomegalovirus: a case report

Pneumocystis jirovecii, Cytomegalovirus and varicella-zoster virus are all opportunistically infective pathogens, but pulmonary co-infection with these pathogens is rare. Herein, this case report describes a patient with autoimmune haemolytic anaemia treated with methylprednisolone and cyclosporine that presented with rapidly progressive severe respiratory failure. Analysis of microbial nucleic acid sequences in both blood and sputum using next-generation sequencing revealed pulmonary co-infection with Pneumocystis jirovecii, varicella-zoster virus, and possibly Cytomegalovirus. After timely targeted and supportive treatments, the patient recovered. This case report highlights the imaging features of co-infection with these pathogens, the importance of next-generation sequencing for early diagnosis in immunosuppressed patients, and the effects of corticosteroid therapy.

InRFNet: Involution Receptive Field Network for COVID-19 Diagnosis

COVID-19 is an emerging infectious disease that has been rampant worldwide since its onset causing Lung irregularity and severe respiratory failure due to pneumonia. The Community-Acquired Pneumonia (CAP), Normal, and COVID-19 Computed Tomography (CT) scan images are classified using Involution Receptive Field Network from Large COVID-19 CT scan slice dataset. The proposed lightweight Involution Receptive Field Network (InRFNet) is spatial specific and channel-agnostic with Receptive Field structure to enhance the feature map extraction. The InRFNet model evaluation results show high training (99%) and validation (96%) accuracy. The performance metrics of the InRFNet model are Sensitivity (94.48%), Specificity (97.87%), Recall (96.34%), F1-score (96.33%), kappa score (94.10%), ROC-AUC (99.41%), mean square error (0.04), and the total number of parameters (33100).

Elevated TAT in COVID-19 Patients with Normal D-Dimer as a Predictor of Severe Respiratory Failure: A Retrospective Analysis of 797 Patients

Although previous studies have revealed that elevated D-dimer in the early stage of coronavirus 2019 (COVID-19) indicates pulmonary intravascular coagulation, the state of coagulation/fibrinolysis disorder with normal D-dimer is unknown. The study aimed to investigate how coagulation/fibrinolysis markers affect severe respiratory failure in the early stage of COVID-19. Among 1043 patients with COVID-19, 797 patients were included in our single-center retrospective study. These 797 patients were divided into two groups, the normal D-dimer and elevated D-dimer groups and analyzed for each group. A logistic regression model was fitted for age, sex, body mass index (BMI) ≥ 30 kg/m2, fibrinogen ≥ 617 mg/dL, thrombin-antithrombin complex (TAT) ≥ 4.0 ng/mL, and plasmin-alpha2-plasmin inhibitor-complex (PIC) > 0.8 µg/mL. A multivariate analysis of the normal D-dimer group demonstrated that being male and TAT ≥ 4.0 ng/mL significantly affected severe respiratory failure. In a multivariate analysis of the elevated D-dimer group, BMI ≥ 30 kg/m2 and fibrinogen ≥ 617 mg/dL significantly affected severe respiratory failure. The elevated PIC did not affect severe respiratory failure in any group. Our study demonstrated that hypercoagulation due to SARS-CoV-2 infection may occur even during a normal D-dimer level, causing severe respiratory failure in COVID-19.

Successful treatment of COVID-19-related acute respiratory distress syndrome with rare blood type: A case report

A 62-year-old man with rare blood type exhibited severe respiratory failure due to novel coronavirus. Extracorporeal membrane oxygenation was inapplicable, which requires numerous blood products with the same blood type. We thoroughly restricted fluid volumes by sacrificing renal function. He was discharged with complete recovery of respiratory and renal functions.

Pulmonary fibrosis as an outcome of COVID-19 pneumonia

In this study, we report three cases of persistent severe respiratory failure and radiological signs of diffuse pulmonary fibrosis in patients after COVID-19 related pneumonia. Chest CT criteria for a diagnosis of pulmonary fibrosis include the presence of traction bronchiectasis and parenchymal bands (linear opacities), as well as numerous small subpleural cystic air spaces (honeycombing). The study found that all cases of fibrosis were associated with such risk factors as male gender, old age, and multicomorbidity. Chest CT of one patient with acute respiratory distress syndrome showed radiographic characteristics of pulmonary fibrosis together with the presence of ground glass opacities (GGO) – the main CT feature of COVID-19 pneumonia. In two other patients, CT features of pulmonary fibrosis appeared in about 2 months after the hospital stay.Thus, pulmonary fibrosis is severe and rapidly progressive complication of COVID-19 pneumonia with a poor prognosis, especially in patients with multiple risk factors.