Effect of Tocilizumab on "Ventilator Free Days" Composite Outcome in SARS-CoV-2 Patients: A Retrospective Competing Risk Analysis.

Background: SARS-CoV-2 infection demonstrates a wide range of severity. More severe cases demonstrate a cytokine storm with elevated serum interleukin-6, hence IL-6 receptor antibody tocilizumab was tried for the management of severe cases. Aims: Effect of tocilizumab on ventilator-free days among critically ill SARS-CoV-2 patients. Method: Retrospective propensity score matching study, comparing mechanically ventilated patients who received tocilizumab to a control group. Results: 29 patients in the intervention group were compared to 29 controls. Matched groups were similar. Ventilator-free days were more numerous in the intervention group (SHR 2.7, 95% CI: 1.2 - 6.3; p = 0.02), ICU mortality rate was not different (37.9% versus 62%, p = 0.1), actual ventilator-free periods were significantly longer in tocilizumab group (mean difference 4.7 days; p = 0.02). Sensitivity analysis showed a significantly lower hazard ratio of death in tocilizumab group (HR 0.49, 95% CI: 0.25 - 0.97; p = 0.04). There was no difference in positive cultures among groups (55.2% in tocilizumab group versus 34.5% in the control; p = 0.1). Conclusion: Tocilizumab may improve the composite outcome of ventilator-free days at day 28 among mechanically ventilated SARS-CoV-2 patients; it is associated with significantly longer actual ventilator-free periods, and insignificantly lower mortality and higher superinfection.

Mortality and Pulmonary Embolism in Acute Respiratory Distress Syndrome From COVID-19 vs. Non-COVID-19.

Purpose: There may be a difference in respiratory mechanics, inflammatory markers, and pulmonary emboli in COVID-19 associated ARDS vs. ARDS from other etiologies. Our purpose was to determine differences in respiratory mechanics, inflammatory markers, and incidence of pulmonary embolism in patients with and without COVID-19 associated ARDS admitted in the same period and treated with a similar ventilation strategy. Methods: A cohort study of COVID-19 associated ARDS and non COVID-19 patients in a Saudi Arabian center between June 1 and 15, 2020. We measured respiratory mechanics (ventilatory ratio (VR), recruitability index (RI), markers of inflammation, and computed tomography pulmonary angiograms. Results: Forty-two patients with COVID-19 and 43 non-COVID patients with ARDS comprised the cohort. The incidence of "recruitable" patients using the recruitment/inflation ratio was slightly lower in COVID-19 patients (62 vs. 86%; p = 0.01). Fifteen COVID-19 ARDS patients (35.7%) developed a pulmonary embolism as compared to 4 (9.3%) in other ARDS patients (p = 0.003). In COVID-19 patients, a D-Dimer ≥ 5.0 mcg/ml had a 73% (95% CI 45-92%) sensitivity and 89% (95% CI 71-98%) specificity for predicting pulmonary embolism. Crude 60-day mortality was higher in COVID-19 patients (35 vs. 15%; p = 0.039) but three multivariate analysis showed that independent predictors of 60-day mortality included the ventilatory ratio (OR 3.67, 95% CI 1.61-8.35), PaO2/FIO2 ratio (OR 0.93; 95% CI 0.87-0.99), IL-6 (OR 1.02, 95% CI 1.00-1.03), and D-dimer (OR 7.26, 95% CI 1.11-47.30) but not COVID-19 infection. Conclusion: COVID-19 patients were slightly less recruitable and had a higher incidence of pulmonary embolism than those with ARDS from other etiologies. A high D-dimer was predictive of pulmonary embolism in COVID-19 patients. COVID-19 infection was not an independent predictor of 60-day mortality in the presence of ARDS.

Renal Tubular Acidosis in Critically Ill Patients with Coronavirus Disease 2019 Acute Respiratory Distress Syndrome.

The coronavirus disease 2019 (COVID-19) infection associated with multisystemic involvement including renal manifestations has been described in the literature. The recent data show a high mortality rate of 60%-90% once renal function begins to deteriorate. We report on three patients who were admitted to intensive care unit due to severe COVID-19 acute respiratory distress syndrome and developed distal renal tubular acidosis. The three COVID-19 patients had hyperchloremic acidosis which was investigated thoroughly through a biochemical analysis of arterial blood gases and urine test as well as serological tests for autoimmune diseases and chronic infections, in addition to renal ultrasound. Metabolic acidosis was managed through repeated doses of intravenous sodium bicarbonate therapy; however, continuous renal replacement therapy was initiated for two refractory cases. We found that severe COVID-19 infection may be accompanied by hyperchloremic acidosis due to the cytopathic damage of the distal renal tubules, making the buffering system nonefficient and if not managed adequately, it may lead to poor prognosis.

Erratum: Profili et al. Overview of the User Experience for Snorkeling Mask Designs during the COVID-19 Pandemic. Healthcare 2021, 9, 204.

The authors would like to make the following corrections to the published paper [...].

Peripheral neuropathy in severe COVID-19 resolved with therapeutic plasma exchange.

Peripheral neuropathies including Guillain-Barré syndrome may be linked to life-threatening COVID-19. Plasma exchange is a safe rescue therapy in severe COVID-19 with associated neurological manifestations and thromboinflammation.

Therapeutic plasma exchange in patients with life-threatening COVID-19: a randomised controlled clinical trial.

Assessment of efficacy of therapeutic plasma exchange (TPE) following life-threatening COVID-19. This was an open-label, randomised clinical trial of ICU patients with life-threatening COVID-19 (positive RT-qPCR plus ARDS, sepsis, organ failure, hyperinflammation). Study was terminated after 87/120 patients enrolled. Standard treatment plus TPE (n = 43) versus standard treatment (n = 44), and stratified by PaO2/FiO2 ratio (>150 vs. ≤150), were compared. Primary outcomes were 35-day mortality and TPE safety. Secondary outcomes were association between TPE and mortality, improvement in SOFA score, change in inflammatory biomarkers, days on mechanical ventilation (MV), and ICU length of stay (LOS). Eighty-seven patients [median age 49 (IQR 34-63) years; 82.8% male] were randomised (44 standard care; 43 standard care plus TPE). Days on MV (P = 0.007) and ICU LOS (P = 0.02) were lower in the TPE group. 35-Day mortality was non-significantly lower in the TPE group (20.9% vs. 34.1%; Kaplan-Meier, P = 0.582). TPE was associated with increased lymphocytes and ADAMTS-13 activity and decreased serum lactate, lactate dehydrogenase, ferritin, d-dimers and interleukin-6. Multivariable regression analysis provided several predictors of 35-day mortality: PaO2/FiO2 ratio (HR, 0.98, 95% CI 0.96-1.00; P = 0.02]; ADAMTS-13 activity (HR, 0.89, 95% CI 0.82-0.98; P = 0.01); pulmonary embolism (HR, 3.57, 95% CI 1.43-8.92; P = 0.007). Post-hoc analysis revealed a significant reduction in SOFA score for TPE patients (P < 0.05). In critically-ill COVID-19 patients, addition of TPE to standard ICU therapy was associated with faster clinical recovery and no increased 35-day mortality.

Radiological, epidemiological and clinical patterns of pulmonary viral infections.

Respiratory viruses are the most common causes of acute respiratory infections. However, identification of the underlying viral pathogen may not always be easy. Clinical presentations of respiratory viral infections usually overlap and may mimic those of diseases caused by bacteria. However, certain imaging morphologic patterns may suggest a particular viral pathogen as the cause of the infection. Although definitive diagnosis cannot be made on the basis of clinical or imaging features alone, the use of a combination of clinical and radiographic findings can substantially improve the accuracy of diagnosis. The purpose of this review is to present the clinical, epidemiological and radiological patterns of lower respiratory tract viral pathogens providing a comprehensive approach for their diagnosis and identification in hospitals and community outbreaks.

Overview of the User Experience for Snorkeling Mask Designs during the COVID-19 Pandemic.

During the first wave of the COVID-19 pandemic, industries and academic institutes have collaborated to resolve the worldwide medical supply shortage issues. Innovative designs of 3D-printed items were proposed and developed by the maker community as a temporary solution to address the lack of personal protective equipment. An overview of global ongoing and past initiatives during the COVID-19 pandemic along with their challenges on retrofitting full-face snorkeling masks for healthcare applications such as splash-proof face shields, respirator masks and non-invasive ventilation systems are reported in this contribution. This study reviews these global initiatives and challenges. From our analysis, the present situation highlights the need to build solid networks between healthcare institutes and the different rapid prototyping initiatives. A clear feedback system needs to be implemented to facilitate effective collaboration between engineering (maker) and healthcare teams, to optimize the available human resources, and to achieve adequate product developments responding to the needs of healthcare workers.

A Retrospective Analysis of Thromboembolic Phenomena in Mechanically Ventilated Patients with COVID-19.

BACKGROUND: Recent studies have shown an increased prevalence of thromboembolic disease in critically ill patients with the novel SARS-CoV-2 disease (COVID-19). However, the use of enhanced anticoagulation therapy in these patients remains controversial. OBJECTIVES: To determine the incidence of thromboembolic phenomena (TEP) and hemorrhagic events (HEs) in intensive care unit (ICU) COVID-19 patients. METHODS: One hundred and sixty ICU patients with COVID-19 were enrolled. Clinical examination results, laboratory data, and imaging studies (computed tomography/Doppler ultrasound scans) for these patients were retrospectively collected and analyzed. Outcome measures including days on mechanical ventilation, ICU length of stay, and day-28 mortality were recorded. RESULTS: Sixty patients (37.5%) developed TEP including thirty patients with deep vein thrombosis, 55 patients with pulmonary embolism, and 7 patients with arterial thromboembolism. Cardiac arrhythmias, lymphocytopenia, and increased D-dimers were more frequently observed in the TEP group compared to the non-TEP group of patients (all p < 0.05). The sensitivity, specificity, and positive and negative predictive values of a cutoff D-dimer level of 3.0 µg/mL for predicting PE were 74.5%, 95.1%, 86.8%, and 91.9%, respectively. Thirteen patients experienced HEs, which were more frequently observed in the TEP group (p < 0.05). Twenty-eight-day mortality was higher in the TEP group (60%) compared to the non-TEP group (30%) of patients (p=0.02). CONCLUSIONS: The rates of TEP and HEs in mechanically ventilated critically ill COVID-19 patients were 37. 5% and 8.1%. Twenty-eight-day mortality was higher in the TEP group (60%) compared to the non-TEP group (30%) of patients.

The COVID-19 Worsening Score (COWS)-a predictive bedside tool for critical illness.

OBJECTIVES: To evaluate the accuracy of a new COVID-19 prognostic score based on lung ultrasound (LUS) and previously validated variables in predicting critical illness. METHODS: We conducted a single-center retrospective cohort development and internal validation study of the COVID-19 Worsening Score (COWS), based on a combination of the previously validated COVID-GRAM score (GRAM) variables and LUS. Adult COVID-19 patients admitted to the emergency department (ED) were enrolled. Ten variables previously identified by GRAM, days from symptom onset, LUS findings, and peripheral oxygen saturation/fraction of inspired oxygen (P/F) ratio were analyzed. LUS score as a single predictor was assessed. We evaluated GRAM model's performance, the impact of adding LUS, and then developed a new model based on the most predictive variables. RESULTS: Among 274 COVID-19 patients enrolled, 174 developed critical illness. The GRAM score identified 51 patients at high risk of developing critical illness and 132 at low risk. LUS score over 15 (range 0 to 36) was associated with a higher risk ratio of critical illness (RR, 2.05; 95% confidence interval [CI], 1.52-2.77; area under the curve [AUC], 0.63; 95% CI 0.676-0.634). The newly developed COVID-19 Worsening Score relies on five variables to classify high- and low-risk patients with an overall accuracy of 80% and negative predictive value of 93% (95% CI, 87%-98%). Patients scoring more than 0.183 on COWS showed a RR of developing critical illness of 8.07 (95% CI, 4.97-11.1). CONCLUSIONS: COWS accurately identify patients who are unlikely to need intensive care unit (ICU) admission, preserving resources for the remaining high-risk patients.

COVID-19 with spontaneous pneumothorax, pneumomediastinum, and subcutaneous emphysema in the intensive care unit: Two case reports.

Real-Time-reverse-transcription-Polymerase-Chain-Reaction from nasopharyngeal swabs and chest computed tomography (CT) depicting typically bilateral ground-glass opacities with a peripheral and/or posterior distribution are mandatory in the diagnosis of COVID-19. COVID-19 pneumonia may present though with atypical features such as pleural and pericardial effusions, lymphadenopathy, cavitations, and CT halo sign. In these two case-reports, COVID-19 presented as pneumothorax, pneumomediastinum and subcutaneous emphysema in critically ill patients. These disorders may require treatment or can be even self-limiting. Clinicians should be aware of their potential effects on the cardiorespiratory status of critically ill COVID-19 patients. Finally, pneumothorax can be promptly diagnosed by means of lung ultrasound. Although operator dependent, lung ultrasound is a useful bedside diagnostic tool that could alleviate the risk of cross-infection related to COVID-19 patient transport.

Plasma exchange in the treatment of complex COVID-19-related critical illness: controversies and perspectives.

COVID-19 (coronavirus disease 2019), caused by the novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), emerged in Wuhan, China, and has spread worldwide, resulting in over 73 million cases and more than 1 600 000 deaths as of December 2020. Although the disease is asymptomatic in most cases, some patients develop life-threatening disease characterised by acute respiratory distress syndrome, sepsis, multisystem organ failure (MSOF), extrapulmonary manifestations, thromboembolic disease and associated cytokine release syndrome. The rationale for applying therapeutic plasma exchange (TPE) early in the course of fulminant COVID-19 is the suppression of thromboinflammation and amelioration of microangiopathy, thus preventing the ensuing MSOF. In the course of complicated critical illness due to COVID-19, immune dysregulation may be as important as viral replication itself. Moreover, the natural course of SARS-CoV-2 infection remains obscure, as re-infections and/or recurrently positive real-time PCR results have been reported. Although concerns still exist regarding its potential immunosuppressive effects and safety, TPE shows promise in the management of life-threatening COVID-19 as documented by various pilot studies, which remain to be confirmed by future randomised controlled trials. However, current data suggest that TPE could be an adjunctive rescue therapy in complex COVID-19 critical illness.

Continuous renal replacement therapy with the addition of CytoSorb cartridge in critically ill patients with COVID-19 plus acute kidney injury: A case-series.

Our aim was to investigate continuous renal replacement therapy (CRRT) with CytoSorb cartridge for patients with life-threatening COVID-19 plus acute kidney injury (AKI), sepsis, acute respiratory distress syndrome (ARDS), and cytokine release syndrome (CRS). Of 492 COVID-19 patients admitted to our intensive care unit (ICU), 50 had AKI necessitating CRRT (10.16%) and were enrolled in the study. Upon ICU admission, all had AKI, ARDS, septic shock, and CRS. In addition to CRRT with CytoSorb, all received ARDS-net ventilation, prone positioning, plus empiric ribavirin, interferon beta-1b, antibiotics, hydrocortisone, and prophylactic anticoagulation. We retrospectively analyzed inflammatory biomarkers, oxygenation, organ function, duration of mechanical ventilation, ICU length-of-stay, and mortality on day-28 post-ICU admission. Patients were 49.64 ± 8.90 years old (78% male) with body mass index of 26.70 ± 2.76 kg/m2 . On ICU admission, mean Acute Physiology and Chronic Health Evaluation (APACHE) II was 22.52 ± 1.1. Sequential Organ Function Assessment (SOFA) score was 9.36 ± 2.068 and the ratio of partial arterial pressure of oxygen to fractional inspired concentration of oxygen (PaO2 /FiO2 ) was 117.46 ± 36.92. Duration of mechanical ventilation was 17.38 ± 7.39 days, ICU length-of-stay was 20.70 ± 8.83 days, and mortality 28 days post-ICU admission was 30%. Nonsurvivors had higher levels of inflammatory biomarkers, and more unresolved shock, ARDS, AKI, and pulmonary emboli (8% vs. 4%, P < .05) compared to survivors. After 2 ± 1 CRRT sessions with CytoSorb, survivors had decreased SOFA scores, lactate dehydrogenase, ferritin, D-dimers, C-reactive protein, and interleukin-6; and increased PaO2 /FiO2 ratios, and lymphocyte counts (all P < .05). Receiver-operator-curve analysis showed that posttherapy values of interleukin-6 (cutoff point >620 pg/mL) predicted in-hospital mortality for critically ill COVID-19 patients (area-under-the-curve: 0.87, 95% CI: 0.81-0.93; P = .001). No side effects of therapy were recorded. In this retrospective case-series, CRRT with the CytoSorb cartridge provided a safe rescue therapy in life-threatening COVID-19 with associated AKI, ARDS, sepsis, and hyperinflammation.

Tocilizumab in the treatment of rapidly evolving COVID-19 pneumonia and multifaceted critical illness: A retrospective case series.

BACKGROUND: COVID-19 associated critical illness characterized by rapidly evolving acute respiratory failure (ARF) can develop, especially on the grounds of hyperinflammation. AIM AND METHODS: A case-series of 61 patients admitted to our intensive care unit (ICU) between August 12 and September 12, 2020 with confirmed COVID-19 pneumonia and rapidly evolving ARF requiring oxygen support therapy and/or mechanical ventilation was retrospectively analyzed. We examined whether intravenous administration of tocilizumab, a monoclonal interleukin-6 receptor antibody, was associated with improved outcome. All patients received empiric antivirals, dexamethasone 6 mg/day for 7 days, antibiotics, and prophylactic anticoagulation. Tocilizumab was administered at a dosage of 8 mg/kg [two consecutive intravenous infusions 12 h apart]. Outcome measures such as mortality on day-14, ICU length of stay, and rate of nosocomial acquired bacterial infections were also analyzed. Results: Patients were males (88.2%) aged 51 [interquartile range (IQR): 42.5-58.75)], with admission Acute Physiology and Chronic Health Evaluation (APACHE) 4 score of 53 (IQR: 37.75-72.5), and had more than one comorbidity (62.3%). On admission, twenty nine patients (47.5%) were mechanically ventilated, and thirty two patients (52.5%) were receiving oxygen therapy. No serious adverse effects due to tocilizumab therapy were recorded. However, twelve patients (19.6%) developed nosocomial acquired infections. ICU length of stay was 13 (IQR: 9-17) days, and mortality on day-14 was 24.6%. Six patients were shifted to other hospitals but were followed-up. The overall mortality on day-30 was 31.1%. Non-mechanically ventilated patients had higher survival rates compared to mechanically ventilated patients although results were not significant [hazards ratio = 2.6 (95% confidence intervals: 0.9-7.7), p = 0.08]. Tocilizumab did not affect the mortality of critically ill COVID-19 patients. CONCLUSION: Tocilizumab could be an adjunct safe therapy in rapidly evolving COVID-19 pneumonia and associated critical illness.