Publications by authors named "Dimitrios Karakitsos"

111 Publications

Optic Nerve Sheath Diameter Ultrasound for Raised Intracranial Pressure: A Literature Review and Meta-analysis of its Diagnostic Accuracy.

J Ultrasound Med 2021 Apr 24. Epub 2021 Apr 24.

Department of Internal Medicine, University of South Carolina, School of Medicine, Columbia, South Carolina, USA.

Optic nerve sheath diameter (ONSD) ultrasound is becoming increasingly more popular for estimating raised intracranial pressure (ICP). We performed a systematic review and analysis of the diagnostic accuracy of ONSD when compared to the standard invasive ICP measurement.

Method: We performed a systematic search of PUBMED and EMBASE for studies including adult patients with suspected elevated ICP and comparing sonographic ONSD measurement to a standard invasive method. Quality of studies was assessed using the QUADAS-2 tool by two independent authors. We used a bivariate model of random effects to summarize pooled sensitivity, specificity, and diagnostic odds ratio (DOR). Heterogeneity was investigated by meta-regression and sub-group analyses.

Results: We included 18 prospective studies (16 studies including 619 patients for primary outcome). Only one study was of low quality, and there was no apparent publication bias. Pooled sensitivity was 0.9 [95% confidence intervals (CI): 0.85-0.94], specificity was 0.85 (95% CI: 0.8-0.89), and DOR was 46.7 (95% CI: 26.2-83.2) with partial evidence of heterogeneity. The Area-Under-the-Curve of the summary Receiver-Operator-Curve was 0.93 (95% CI: 0.91-0.95, P < .05). No covariates were significant in the meta-regression. Subgroup analysis of severe traumatic brain injury and parenchymal ICP found no heterogeneity. ICP and ONSD had a correlation coefficient of 0.7 (95% CI: 0.63-0.76, P < .05).

Conclusion: ONSD is a useful adjunct in ICP evaluation but is currently not a replacement for invasive methods where they are feasible.
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http://dx.doi.org/10.1002/jum.15732DOI Listing
April 2021

Delayed intensive care unit admission from the emergency department: impact on patient outcomes. A retrospective study.

Rev Bras Ter Intensiva 2021 Jan-Mar;33(1):125-137

Department of Critical Care, King Saud Medical City - Riyadh, Arábia Saudita.

Objective: To study the impact of delayed admission by more than 4 hours on the outcomes of critically ill patients.

Methods: This was a retrospective observational study in which adult patients admitted directly from the emergency department to the intensive care unit were divided into two groups: Timely Admission if they were admitted within 4 hours and Delayed Admission if admission was delayed for more than 4 hours. Intensive care unit length of stay and hospital/intensive care unit mortality were compared between the groups. Propensity score matching was performed to correct for imbalances. Logistic regression analysis was used to explore delayed admission as an independent risk factor for intensive care unit mortality.

Results: During the study period, 1,887 patients were admitted directly from the emergency department to the intensive care unit, with 42% being delayed admissions. Delayed patients had significantly longer intensive care unit lengths of stay and higher intensive care unit and hospital mortality. These results were persistent after propensity score matching of the groups. Delayed admission was an independent risk factor for intensive care unit mortality (OR = 2.6; 95%CI 1.9 - 3.5; p < 0.001). The association of delay and intensive care unit mortality emerged after a delay of 2 hours and was highest after a delay of 4 hours.

Conclusion: Delayed admission to the intensive care unit from the emergency department is an independent risk factor for intensive care unit mortality, with the strongest association being after a delay of 4 hours.
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http://dx.doi.org/10.5935/0103-507X.20210014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8075331PMC
March 2020

COVID-19 air travel restrictions and vaccine passports: An ongoing debate.

Travel Med Infect Dis 2021 Apr 20;42:102049. Epub 2021 Apr 20.

Critical Care Department, King Saud Medical City, Riyadh, Saudi Arabia; Department of Internal Medicine, University of South Carolina, School of Medicine, Columbia, SC, USA. Electronic address:

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http://dx.doi.org/10.1016/j.tmaid.2021.102049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056875PMC
April 2021

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

Int J Antimicrob Agents 2021 May 7;57(5):106334. Epub 2021 Apr 7.

Research & Innovation Centre, King Saud Medical City, Riyadh, Saudi Arabia; Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA. Electronic address:

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 PaO/FiO 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: PaO/FiO 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.
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http://dx.doi.org/10.1016/j.ijantimicag.2021.106334DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024223PMC
May 2021

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

Healthcare (Basel) 2021 Feb 14;9(2). Epub 2021 Feb 14.

Department of Mechanical Engineering, École de Technologie Supérieure, 1100 rue Notre-Dame Ouest, Montreal, QC H3C 1K3, Canada.

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.
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http://dx.doi.org/10.3390/healthcare9020204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917645PMC
February 2021

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

J Infect Public Health 2021 Mar 29;14(3):290-292. Epub 2020 Dec 29.

Critical Care Department, King Saud Medical City, Riyadh, Saudi Arabia; Critical Care Department. Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. Electronic address:

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.
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http://dx.doi.org/10.1016/j.jiph.2020.12.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7771902PMC
March 2021

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

Crit Care Res Pract 2021 8;2021:8737580. Epub 2021 Jan 8.

Critical Care Department, King Saud Medical City, Riyadh, Saudi Arabia.

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 < 0.05). The sensitivity, specificity, and positive and negative predictive values of a cutoff D-dimer level of 3.0 g/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 ( < 0.05). Twenty-eight-day mortality was higher in the TEP group (60%) compared to the non-TEP group (30%) of patients (=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.
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http://dx.doi.org/10.1155/2021/8737580DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7805521PMC
January 2021

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

Echocardiography 2021 02 24;38(2):207-216. Epub 2021 Jan 24.

Department of Medicine, University of Udine, Udine, Italy.

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.
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http://dx.doi.org/10.1111/echo.14962DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8013873PMC
February 2021

Radiological, epidemiological and clinical patterns of pulmonary viral infections.

Eur J Radiol 2021 Mar 14;136:109548. Epub 2021 Jan 14.

Department of Thoracic Radiology, Division of Diagnostic Imaging. University of Texas MD Anderson Cancer Center, Houston, TX, USA.

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.
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http://dx.doi.org/10.1016/j.ejrad.2021.109548DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7808729PMC
March 2021

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

Int J Antimicrob Agents 2021 Feb 25;57(2):106273. Epub 2020 Dec 25.

Critical Care Department, King Saud Medical City, Riyadh, Saudi Arabia; Critical Care Department, Keck School of Medicine, USC, Los Angeles, CA, USA.

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.
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http://dx.doi.org/10.1016/j.ijantimicag.2020.106273DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834644PMC
February 2021

Co-infection of human immunodeficiency virus, herpes simplex virus-2 and SARS-CoV-2 with false-negative real-time polymerase chain reaction.

Singapore Med J 2020 Nov 30. Epub 2020 Nov 30.

Critical Care Department, King Saud Medical City, Riyadh, Kingdom of Saudi Arabia.

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http://dx.doi.org/10.11622/smedj.2020158DOI Listing
November 2020

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

Clin Case Rep 2020 Oct 7. Epub 2020 Oct 7.

Critical Care Department King Saud Medical City Riyadh Saudi Arabia.

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.
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http://dx.doi.org/10.1002/ccr3.3397DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7675564PMC
October 2020

Leadership to prevent COVID-19: is it the most important mitigation factor?

Travel Med Infect Dis 2020 Nov - Dec;38:101925. Epub 2020 Nov 20.

Critical Care Department, King Saud Medical City, Riyadh, Saudi Arabia; University of South Carolina, School of Medicine, Columbia, SC, USA. Electronic address:

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http://dx.doi.org/10.1016/j.tmaid.2020.101925DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678417PMC
January 2021

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

Artif Organs 2021 May 26;45(5):E101-E112. Epub 2020 Dec 26.

Critical Care Department, King Saud Medical City, Riyadh, Saudi Arabia.

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/m . 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 (PaO /FiO ) 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 PaO /FiO 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.
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http://dx.doi.org/10.1111/aor.13864DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753655PMC
May 2021

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

J Ultrasound Med 2020 Nov 13. Epub 2020 Nov 13.

Department of Emergency Medicine, St. Francis Hospital, Columbus, Georgia, USA.

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 = 0.048), 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 = 0.03) were mortality predictors. Non-survivors had increased incidence of pulmonary abnormalities (B-lines, pleural line irregularities, and consolidations) compared to survivors (p < 0.05). 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.
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http://dx.doi.org/10.1002/jum.15563DOI Listing
November 2020

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

Ann Med Surg (Lond) 2020 Dec 5;60:417-424. Epub 2020 Nov 5.

Research & Innovation Centre, King Saud Medical City, Riyadh, Saudi Arabia.

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.
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http://dx.doi.org/10.1016/j.amsu.2020.10.061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7642808PMC
December 2020

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.

SAGE Open Med Case Rep 2020 8;8:2050313X20964089. Epub 2020 Oct 8.

Critical Care Department, King Saud Medical City, Riyadh, Saudi Arabia.

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 Optia 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-β2-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.
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http://dx.doi.org/10.1177/2050313X20964089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7550946PMC
October 2020

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

J Epidemiol Glob Health 2021 03 3;11(1):98-104. Epub 2020 Oct 3.

Research & Innovation Centre King Saud Medical City, Ministry of Health, Riyadh, Saudi Arabia.

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 (SpO/FiO) 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 SpO/FiO 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 SpO/FiO ratio, and increased lactate and D-dimers were predictors of 28-day mortality in critically ill COVID-19 patients.
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http://dx.doi.org/10.2991/jegh.k.200928.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7958266PMC
March 2021

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

Respir Med Case Rep 2020 15;31:101252. Epub 2020 Oct 15.

Critical Care Department, King Saud Medical City, Riyadh, Saudi Arabia.

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.
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http://dx.doi.org/10.1016/j.rmcr.2020.101252DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7557168PMC
October 2020

Helmet Continuous Positive Airway Pressure in the Treatment of COVID-19 Patients with Acute Respiratory Failure could be an Effective Strategy: A Feasibility Study.

J Epidemiol Glob Health 2020 Sep;10(3):201-203

Senior Infectious Diseases Consultant & Director Research & Innovation Center, King Saud Medical City, Ministry of Health, Riyadh, Saudi Arabia.

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http://dx.doi.org/10.2991/jegh.k.200817.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7509101PMC
September 2020

Fulminant septic shock due to Edwardsiella tarda infection associated with multiple liver abscesses: a case report and review of the literature.

J Med Case Rep 2020 Sep 9;14(1):144. Epub 2020 Sep 9.

Critical Care Department, King Saud Medical City, Riyadh, Saudi Arabia.

Introduction: Edwardsiella tarda uncommonly infects humans. The usual presentation is mild gastroenteritis, but systemic manifestations may occur. Lethal infections are rarely documented in patients with underlying disorders.

Case Presentation: A previously healthy 37-year-old Southeast Asian woman presented to our hospital with recent onset of abdominal pain, fever, and vomiting. Her condition rapidly deteriorated with signs and symptoms of fulminant septic shock; thus, she was intubated, supported with intravenous vasopressors and fluids, and transferred to the intensive care unit. An abdominal computed tomographic scan with contrast revealed multiple liver abscesses. Blood cultures were obtained and computed tomography-guided percutaneous drainage of the liver abscesses with supplementary cultures was performed; thereafter, empirical broad-spectrum antibiotics were initiated. All cultures grew E. tarda, whereas an antibiogram showed resistance to broad-spectrum antibiotics and sensitivity to ciprofloxacin and aminoglycosides; thus, the antibiotic regimen was updated accordingly. The patient made an uneventful recovery and was discharged from the intensive care unit 14 days after admission.

Conclusion: E. tarda human infection can present as liver abscess and fulminant septic shock. E. tarda strains can be resistant to broad-spectrum antibiotics; hence, culture-based antibiotics should be used accordingly. Clinicians should be aware of this rare and potentially lethal infection.
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http://dx.doi.org/10.1186/s13256-020-02469-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7478901PMC
September 2020

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

Respir Med Case Rep 2020 28;31:101203. Epub 2020 Aug 28.

Critical Care Department, King Saud Medical City, Riyadh, Saudi Arabia.

This is the first reported case, to our knowledge, of co-infection of and SARS-CoV-2 in a young patient with underlying idiopathic bronchiectasis and vitamin D 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.
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http://dx.doi.org/10.1016/j.rmcr.2020.101203DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7452825PMC
August 2020

Reverse takotsubo cardiomyopathy in fulminant COVID-19 associated with cytokine release syndrome and resolution following therapeutic plasma exchange: a case-report.

BMC Cardiovasc Disord 2020 08 26;20(1):389. Epub 2020 Aug 26.

Critical Care Department, King Saud Medical City, Riyadh, Kingdom of Saudi Arabia.

Background: Fulminant (life-threatening) COVID-19 can be associated with acute respiratory failure (ARF), multi-system organ failure and cytokine release syndrome (CRS). We present a rare case of fulminant COVID-19 associated with reverse-takotsubo-cardiomyopathy (RTCC) that improved with therapeutic plasma exchange (TPE).

Case Presentation: A 40 year old previous healthy male presented in the emergency room with 4 days of dry cough, chest pain, myalgias and fatigue. He progressed to ARF requiring high-flow-nasal-cannula (flow: 60 L/minute, fraction of inspired oxygen: 40%). Real-Time-Polymerase-Chain-Reaction (RT-PCR) assay confirmed COVID-19 and chest X-ray showed interstitial infiltrates. Biochemistry suggested CRS: increased C-reactive protein, lactate dehydrogenase, ferritin and interleukin-6. Renal function was normal but lactate levels were elevated. Electrocardiogram demonstrated non-specific changes and troponin-I levels were slightly elevated. Echocardiography revealed left ventricular (LV) basal and midventricular akinesia with apex sparing (LV ejection fraction: 30%) and depressed cardiac output (2.8 L/min) consistent with a rare variant of stress-related cardiomyopathy: RTCC. His ratio of partial arterial pressure of oxygen to fractional inspired concentration of oxygen was < 120. He was admitted to the intensive care unit (ICU) for mechanical ventilation and vasopressors, plus antivirals (lopinavir/ritonavir), and prophylactic anticoagulation. Infusion of milrinone failed to improve his cardiogenic shock (day-1). Thus, rescue TPE was performed using the Spectra Optia™ Apheresis System equipped with the Depuro D2000 Adsorption Cartridge (Terumo BCT Inc., USA) without protective antibodies. Over 5 days he received daily TPE (each lasting 4 hours). His lactate levels, oxygenation, and LV function normalized and he was weaned off vasopressors. His inflammation markers improved, and he was extubated on day-7. RT-PCR was negative on day-17. He was discharged to home isolation in good condition.

Conclusion: Stress-cardiomyopathy may complicate the course of fulminant COVID-19 with associated CRS. If inotropic therapy fails, TPE without protective antibodies may help rescue the critically ill patient.
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http://dx.doi.org/10.1186/s12872-020-01665-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7447602PMC
August 2020

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

Respir Med Case Rep 2020 11;31:101186. Epub 2020 Aug 11.

Critical Care Department, King Saud Medical City, Riyadh, Saudi Arabia.

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.
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http://dx.doi.org/10.1016/j.rmcr.2020.101186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7418650PMC
August 2020

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

J Ultrasound Med 2021 Mar 14;40(3):443-456. Epub 2020 Aug 14.

Department of Medicine, University of South Carolina School of Medicine, Columbia, South Carolina, USA.

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.
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http://dx.doi.org/10.1002/jum.15417DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7436430PMC
March 2021

Fragile Endothelium and Brain Dysregulated Neurochemical Activity in COVID-19.

ACS Chem Neurosci 2020 08 27;11(15):2159-2162. Epub 2020 Jul 27.

Critical Care Department, King Saud Medical City, Riyadh, Saudi Arabia.

Immune system and renin-angiotensin-aldosterone system dysregulation with associated cytokine release syndrome may be a key feature of early stage of SARS-CoV-2 organotropism and infection. Following viral mediated brain injury, dysregulated neurochemical activity may cause neurogenic stress cardiomyopathy, which is characterized by transient myocardial dysfunction and arrhythmias. Cardiomyopathy along with acute acute inflammatory thromboembolism and endotheliitis (fragile endothelium) might at least partially explain the underlying mechanisms of rapidly evolving life-threatening COVID-19. Further studies are clearly required to explore these complex pathologies.
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http://dx.doi.org/10.1021/acschemneuro.0c00437DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7393674PMC
August 2020

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

Am J Emerg Med 2021 Mar 30;41:261.e1-261.e3. Epub 2020 Jul 30.

Critical Care Department, King Saud Medical City, Riyadh, Saudi Arabia; University of South Carolina, School of Medicine, Columbia, SC, USA. Electronic address:

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.
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http://dx.doi.org/10.1016/j.ajem.2020.07.068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7392155PMC
March 2021

Therapeutic plasma exchange in adult critically ill patients with life-threatening SARS-CoV-2 disease: A pilot study.

J Crit Care 2020 12 31;60:328-333. Epub 2020 Jul 31.

Critical Care Department, King Saud Medical City, Riyadh, Saudi Arabia; Department of Internal Medicine, South Carolina University, School of Medicine, Columbia, SC, USA; Critical Care Department, Keck Medical School, USC, LA, CA, USA. Electronic address:

Purpose: We investigated the effect of therapeutic plasma exchange (TPE) on life-threatening COVID-19; presenting as acute respiratory distress syndrome (ARDS) plus multi-system organ failure and cytokine release syndrome (CRS).

Materials And Methods: We prospectively enrolled ten consecutive adult intensive care unit (ICU) subjects [7 males; median age: 51 interquartile range (IQR): 45.1-55.9 years old] with life-threatening COVID-19 infection. All had ARDS [PaO2/FiO2 ratio: 110 (IQR): 95.5-135.5], septic shock, CRS and deteriorated within 24 h of ICU admission despite fluid resuscitation, antibiotics, hydroxychloroquine, ARDS-net and prone position mechanical ventilation. All received 5-7 TPE sessions (dosed as 1.0 to 1.5 plasma volumes).

Results: All of the following significantly normalized (p < 0.05) following the TPE completion, when compared to baseline: Sequential Organ Function Assessment score, PaO2/FiO2 ratio, levels of lymphocytes, total bilirubin, lactate dehydrogenase, ferritin, C-reactive protein and interleukin-6. No adverse effects from TPE were observed. Acute kidney injury and pulmonary embolism were observed in 10% and 20% of patients, respectively. The duration of mechanical ventilation was 9 (IQR: 7 to 12) days, the ICU length of stay was 15 (IQR: 13.2 to 19.6) days and the mortality on day-28 was 10%.

Conclusion: TPE demonstrates a potential survival benefit and low risk in life-threatening COVID-19, albeit in a small pilot study.
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http://dx.doi.org/10.1016/j.jcrc.2020.07.001DOI Listing
December 2020

Comment on Hu et al: The cytokine storm and COVID-19.

J Med Virol 2021 02 21;93(2):631-633. Epub 2020 Aug 21.

Department of Critical Care, King Saud Medical City, Riyadh, Saudi Arabia.

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http://dx.doi.org/10.1002/jmv.26396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7436490PMC
February 2021