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.

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.

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.

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.

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.

Residual Lung Injury in Patients Recovering From COVID-19 Critical Illness: A Prospective Longitudinal Point-of-Care Lung Ultrasound Study.

Scarce data exist regarding the natural history of lung lesions detected on ultrasound in those who survive severe COVID-19 pneumonia. OBJECTIVE: We performed a prospective analysis of point-of-care ultrasound (POCUS) findings in critically ill COVID-19 patients during and after hospitalization. METHODS: We enrolled 171 COVID-19 intensive care unit patients. POCUS of the lungs was performed with phased array (2-4 MHz), convex (2-6 MHz) and linear (10-15 MHz) transducers, scanning 12 lung areas. Chest computed tomography angiography was performed to exclude suspected pulmonary embolism. Survivors were clinically and sonographically evaluated during a 4 month period for evidence of residual lung injury. Chest computed tomography angiography and echocardiography were used to exclude pulmonary hypertension (PH) and chest high-resolution-computed-tomography to exclude interstitial lung disease (ILD) in symptomatic survivors. RESULTS: Cox regression analysis showed that lymphocytopenia (hazard ratio [HR]: 0.88, 95% confidence intervals [CI]: 0.68-0.96, p = .048), increased lactate (HR: 1.17, 95% CI: 0.94-1.46, p = 0.049), and D-dimers (HR: 1.21, 95% CI: 1.03-1.44, p = .03) were mortality predictors. Non-survivors had increased incidence of pulmonary abnormalities (B-lines, pleural line irregularities, and consolidations) compared to survivors (p < .05). During follow-up, POCUS with clinical and laboratory parameters integrated in the semi-quantitative Riyadh-Residual-Lung-Injury scale had sensitivity of 0.82 (95% CI: 0.76-0.89) and specificity of 0.91 (95% CI: 0.94-0.95) in predicting ILD. The prevalence of PH and ILD (non-specific-interstitial-pneumonia) was 7% and 11.8%, respectively. CONCLUSION: POCUS showed ability to monitor the evolution of severe COVID-19 pneumonia after hospital discharge, supporting its integration in clinical predictive models of residual lung injury.

Clinical Characteristics and Predictors of 28-Day Mortality in 352 Critically Ill Patients with COVID-19: A Retrospective Study.

BACKGROUND: Since the first COVID-19 patient in Saudi Arabia (March, 2020) more than 338,539 cases and approximately 4996 dead were reported. We present the main characteristics and outcomes of critically ill COVID-19 patients that were admitted in the largest Ministry of Health Intensive Care Unit (ICU) in Saudi Arabia. METHODS: This retrospective study, analyzed routine epidemiologic, clinical, and laboratory data of COVID-19 critically ill patients in King Saud Medical City (KSMC), Riyadh, Saudi Arabia, between March 20, 2020 and May 31, 2020. Severe acute respiratory syndrome coronavirus-2 infection was confirmed by real-time reverse transcriptase polymerase chain reaction assays performed on nasopharyngeal swabs in all enrolled cases. Outcome measures such as 28-days mortality, duration of mechanical ventilation, and ICU length of stay were analyzed. RESULTS: Three-hundred-and-fifty-two critically ill COVID-19 patients were included in the study. Patients had a mean age of 50.63 ± 13.3 years, 87.2% were males, and 49.4% were active smokers. Upon ICU admission, 56.8% of patients were mechanically ventilated with peripheral oxygen saturation/fraction of inspired oxygen (SpO2/FiO2) ratio of 158 ± 32. No co-infections with other endemic viruses were observed. Duration of mechanical ventilation was 16 (IQR: 8-28) days; ICU length of stay was 18 (IQR: 9-29) days, and 28-day mortality was 32.1%. Multivariate regression analysis showed that old age [Odds Ratio (OR): 1.15, 95% Confidence Intervals (CI): 1.03-1.21], active smoking [OR: 3, 95% CI: 2.51-3.66], pulmonary embolism [OR: 2.91, 95% CI: 2.65-3.36), decreased SpO2/FiO2 ratio [OR: 0.94, 95% CI: 0.91-0.97], and increased lactate [OR: 3.9, 95% CI: 2.4-4.9], and D-dimers [OR: 2.54, 95% CI: 1.57-3.12] were mortality predictors. CONCLUSION: Old age, active smoking, pulmonary embolism, decreased SpO2/FiO2 ratio, and increased lactate and D-dimers were predictors of 28-day mortality in critically ill COVID-19 patients.

Life-threatening COVID-19 presenting as stroke with antiphospholipid antibodies and low ADAMTS-13 activity, and the role of therapeutic plasma exchange: A case series.

We present a case series of three patients with COVID-19 who were admitted to our intensive care unit due to acute respiratory distress syndrome, brain infarction, pulmonary embolism, and antiphospholipid antibodies. We applied therapeutic plasma exchange on all cases. On intensive care unit admission, all patients had low (<10) Glasgow Coma Scale, and central nervous imaging showed multiple brain infarctions. COVID-19 was confirmed by reverse transcriptase polymerase chain reaction assays. Patients underwent rescue therapeutic plasma exchange using the Spectra OptiaTM Apheresis System (Terumo BCT Inc., USA), which operates with acid-citrate dextrose anticoagulant as per Kidney Disease Improving Global Outcomes 2019 guidelines. A dose of 1.5 plasma volume was used for the first dose and then 1 plasma volume daily for a total of five doses. Plasma was replaced with Octaplas LG® (Octapharma AG, USA), which is an artificial fresh frozen plasma product that has undergone viral inactivation by prion reduction technology. We administered ARDS-net/prone positioning ventilation, empiric antiviral treatment, therapeutic anticoagulation, and intensive care unit supportive care. Laboratory tests showed lymphocytopenia; elevated levels of D-dimer, fibrinogen, total bilirubin, C-reactive protein, lactate dehydrogenase, and ferritin; as well as low levels of ADAMTS-13 activity and antibody. Serology tests depicted positive IgM and IgG antiphospholipid antibodies (anti-cardiolipin and anti-ß2-glycoprotein I antibodies). No side effects of therapeutic plasma exchange were recorded. After the completion of therapeutic plasma exchange, patients improved clinically and gradually recovered neurologically (after 27-32 days). To conclude, in life-threatening COVID-19, especially when immune dysregulation features such as antiphospholipid antibodies exist, therapeutic plasma exchange could be an effective rescue therapy.

COVID-19 in a patient with a flare of systemic lupus erythematosus: A rare case-report.

This is a rare case-report of a young female with systemic lupus erythematosus and end-stage kidney disease (on maintenance hemodialysis) who was admitted to our intensive care unit due to life-threatening COVID-19. The patient was diagnosed with a flare of lupus; while being on maintenance hydroxychloroquine therapy. However, after the administration of steroids she made an uneventful recovery and was discharged home. In this report, the diagnostic dilemmas and the therapeutic challenges due to the overlapping clinical, imaging, and laboratory findings between lupus and COVID-19 pneumonitis are outlined. In conclusion, patients with lupus may be affected by COVID-19 despite the administration of hydroxychloroquine. The administration of steroids may have a beneficial effect on mitigating both the flare of SLE and the COVID-19 associated hyperinflammation.

Co-infection of SARS-CoV-2 and Bordetella bronchiseptica in a young man with idiopathic non-cystic bronchiectasis and vitamin D3 deficiency.

This is the first reported case, to our knowledge, of co-infection of Bordetella bronchiseptica and SARS-CoV-2 in a young patient with underlying idiopathic bronchiectasis and vitamin D3 deficiency that was treated successfully with a combination therapeutic regime integrating doxycycline, empiric therapies for COVID-19, vitamin D supplementation, and supportive ICU care. Large prospective studies are required to investigate further the role of co-infections in COVID-19 patients with bronchiectasis. Randomized control trials should examine the putative beneficial role of vitamin D supplementation in patients with COVID-19.

Prospective Longitudinal Evaluation of Point-of-Care Lung Ultrasound in Critically Ill Patients With Severe COVID-19 Pneumonia.

OBJECTIVES: To perform a prospective longitudinal analysis of lung ultrasound findings in critically ill patients with coronavirus disease 2019 (COVID-19). METHODS: Eighty-nine intensive care unit (ICU) patients with confirmed COVID-19 were prospectively enrolled and tracked. Point-of-care ultrasound (POCUS) examinations were performed with phased array, convex, and linear transducers using portable machines. The thorax was scanned in 12 lung areas: anterior, lateral, and posterior (superior/inferior) bilaterally. Lower limbs were scanned for deep venous thrombosis and chest computed tomographic angiography was performed to exclude suspected pulmonary embolism (PE). Follow-up POCUS was performed weekly and before hospital discharge. RESULTS: Patients were predominantly male (84.2%), with a median age of 43 years. The median duration of mechanical ventilation was 17 (interquartile range, 10-22) days; the ICU length of stay was 22 (interquartile range, 20.2-25.2) days; and the 28-day mortality rate was 28.1%. On ICU admission, POCUS detected bilateral irregular pleural lines (78.6%) with accompanying confluent and separate B-lines (100%), variable consolidations (61.7%), and pleural and cardiac effusions (22.4% and 13.4%, respectively). These findings appeared to signify a late stage of COVID-19 pneumonia. Deep venous thrombosis was identified in 16.8% of patients, whereas chest computed tomographic angiography confirmed PE in 24.7% of patients. Five to six weeks after ICU admission, follow-up POCUS examinations detected significantly lower rates (P < .05) of lung abnormalities in survivors. CONCLUSIONS: Point-of-care ultrasound depicted B-lines, pleural line irregularities, and variable consolidations. Lung ultrasound findings were significantly decreased by ICU discharge, suggesting persistent but slow resolution of at least some COVID-19 lung lesions. Although POCUS identified deep venous thrombosis in less than 20% of patients at the bedside, nearly one-fourth of all patients were found to have computed tomography-proven PE.

Insidious development of pulmonary embolism in asymptomatic patients with COVID-19: Two rare case-reports.

Scarce data exist regarding the clinical sequelae of COVID-19 and/or the prevalence of thromboembolic disease in asymptomatic patients. Surely, there is increased prevalence of thromboembolic disease and pulmonary embolism (PE) in critically ill patients with COVID-19; hence the administration of even enhanced thromboprophylaxis was suggested. However, the administration of regular thromboprophylaxis in asymptomatic outpatients is an entirely different matter. Herein, we present the clinical story of insidious PE development in two asymptomatic COVID-19 female patients. Issues regarding the pathogenesis of thromboembolism in COVID-19 and the clinical management are equally discussed.

Thrombolysis in severe COVID-19 pneumonia with massive pulmonary embolism.

OBJECTIVE: No guidelines exist for the management of massive pulmonary embolism (PE) in COVID-19. We present a COVID-19 patient with refractory acute respiratory syndrome (ARDS), and life-threatening PE who underwent successful thrombolysis. CASE PRESENTATION: A previously healthy 47 year old male was admitted to our hospital due to severe COVID-19 pneumonia [confirmed by Real-Time-Polymerase-Chain-Reaction (RT-PCR)]. He had rapidly evolving ARDS [partial arterial pressure of oxygen to fractional inspired concentration of oxygen ratio: 175], and sepsis. Laboratory results showed lymphocytopenia, and increased D-dimer levels (7.7 µg/ml; normal: 0-0.5 µg/ml). The patient was treated in the intensive care unit. On day-1, ARDS-net/prone positioning ventilation, and empiric anti-COVID treatment integrating prophylactic anticoagulation was administered. On hospital day-2, the patient developed shock with worsening oxygenation. Point-of-care-ultrasound depicted a large thrombus migrating from the right atrium to the pulmonary circulation. Intravenous alteplase (100 mg over 2 h) was administered as rescue therapy. The patient made an uneventful recovery, and was discharged to home isolation (day-20) on oral rivaroxaban. CONCLUSION: Thrombolysis may have a critical therapeutic role for massive PE in COVID-19; however the risk of potential bleeding should not be underestimated. Point-of-care ultrasound has a pivotal role in the management of refractory ARDS in COVID-19.

COVID-19 in a patient with active tuberculosis: A rare case-report.

Scarce data exist about the clinical features of COVID-19 in patients with concomitant active and/or latent tuberculosis (TB). This rare case-report outlines the diagnosis, management and outcome of a sixty year old hypertensive and diabetic patient with serious COVID-19 pneumonia and underlying active TB. The patient was treated successfully in a COVID-19 designated intensive care unit in Saudi Arabia.