Early procalcitonin to predict mortality in critically ill COVID-19 patients: a multicentric cohort study.

BACKGROUND: High levels of procalcitonin (PCT) have been associated with a higher risk of mortality in COVID-19 patients. We explored the prognostic role of early PCT assessment in critically ill COVID-19 patients and whether PCT predictive performance would be influenced by immunosuppression. METHODS: Retrospective multicentric analysis of prospective collected data in COVID-19 patients consecutively admitted to 36 intensive care units (ICUs) in Spain and Andorra from March to June 2020. Adult (>18 years) patients with confirmed COVID-19 and available PCT values (<72 hours from ICU admission) were included. Patients were considered as "no immunosuppression" (NI), "chronic immunosuppression" (CI) and "acute immunosuppression" (AIT if only tocilizumab; AIS if only steroids, AITS if both). The primary outcome was the ability of PCT to predict ICU mortality. RESULTS: Of the 1079 eligible patients, 777 patients were included in the analysis. Mortality occurred in 227 (28%) patients. In the NI group 144 (19%) patients were included, 67 (9%) in the CI group, 66 (8%) in the AIT group, 262 (34%) in the AIS group and 238 (31%) in the AITS group; PCT was significantly higher in non-survivors when compared with survivors (0.64 [0.17-1.44] vs. 0.23 [0.11-0.60] ng/mL; P<0.01); however, in the multivariable analysis, PCT values was not independently associated with ICU mortality. PCT values and ICU mortality were significantly higher in patients in the NI and CI groups. CONCLUSIONS: PCT values are not independent predictors of ICU mortality in COVID-19 patients. Acute immunosuppression significantly reduced PCT values, although not influencing its predictive value.

Use of Sedatives and Neuromuscular-Blocking Agents in Mechanically Ventilated Patients with COVID-19 ARDS.

OBJECTIVES: To assess differences in the use of analgesics, sedatives and neuromuscular-blocking agents (NMBA) in patients with acute respiratory distress syndrome (ARDS) due to COVID-19 or other conditions. METHODS: Retrospective observational cohort study, single-center tertiary Intensive Care Unit. COVID-19 patients with ARDS (March-May 2020) and non-COVID ARDS patients (2017-2020) on mechanical ventilation and receiving sedation for at least 48 h. RESULTS: A total of 39 patients met the inclusion criteria in each group, with similar demographics at baseline. COVID-19 patients had a longer duration of MV (median 22 (IQRs 16-29) vs. 9 (6-18) days; p < 0.01), of sedatives administration (18 (11-22) vs. 5 (4-9) days; p < 0.01) and NMBA therapy (12 (9-16) vs. 3 (2-7) days; p < 0.01). During the first 7 days of sedation, compared to non-COVID patients, COVID patients received more frequently a combination of multiple sedative drugs (76.9% vs. 28.2%; p < 0.01) and a higher NMBA regimen (cisatracurium: 3.0 (2.1-3.7) vs. 1.3 (0.9-1.9) mg/kg/day; p < 0.01). CONCLUSIONS: The duration and consumption of sedatives and NMBA was significantly increased in patients with COVID-19 related ARDS than in non-COVID ARDS. Different sedation strategies and protocols might be needed in COVID-19 patients with ARDS, with potential implications on long-term complications and drugs availability.

Fever management in critically ill COVID-19 patients: a retrospective analysis.

BACKGROUND: Fever has been reported as a common symptom in COVID-19 patients. The aim of the study was to describe the characteristics of COVID-19 critically ill patients with fever and to assess if fever management had an impact on some physiologic variables. METHODS: This is a retrospective monocentric cohort analysis of critically ill COVID-19 patients admitted to the Department of Intensive Care Unit (ICU) of Erasme Hospital, Brussels, Belgium, between March 2020 and May 2020. Fever was defined as body temperature ≥38 °C during the ICU stay. We assessed the independent predictors of fever during ICU stay. We reported the clinical and physiological variables before and after the first treated episode of fever during the ICU stay. RESULTS: A total of 72 critically ill COVID-19 patients were admitted to the ICU over the study period and were all eligible for the final analysis; 53 (74%) of them developed fever, after a median of 4 [0-13] hours since ICU admission. In the multivariable analysis, male gender (OR 5.41 [C.I. 95% 1.34-21.92]; P=0.02) and low PaO2/FiO2 ratio (OR 0.99 [C.I. 95% 0.99-1.00]; P=0.04) were independently associated with fever. After the treatment of the first febrile episode, heart rate and respiratory rate significantly decreased together with an increase in PaO2 and SaO2. CONCLUSIONS: In our study, male gender and severe impairment of oxygenation were independently associated with fever in critically ill COVID-19 patients. Fever treatment reduced heart rate and respiratory rate and improved systemic oxygenation.

Outcome Prediction in Patients with Severe COVID-19 Requiring Extracorporeal Membrane Oxygenation-A Retrospective International Multicenter Study.

The role of veno-venous extracorporeal membrane oxygenation therapy (V-V ECMO) in severe COVID-19 acute respiratory distress syndrome (ARDS) is still under debate and conclusive data from large cohorts are scarce. Furthermore, criteria for the selection of patients that benefit most from this highly invasive and resource-demanding therapy are yet to be defined. In this study, we assess survival in an international multicenter cohort of COVID-19 patients treated with V-V ECMO and evaluate the performance of several clinical scores to predict 30-day survival. METHODS: This is an investigator-initiated retrospective non-interventional international multicenter registry study (NCT04405973, first registered 28 May 2020). In 127 patients treated with V-V ECMO at 15 centers in Germany, Switzerland, Italy, Belgium, and the United States, we calculated the Sequential Organ Failure Assessment (SOFA) Score, Simplified Acute Physiology Score II (SAPS II), Acute Physiology And Chronic Health Evaluation II (APACHE II) Score, Respiratory Extracorporeal Membrane Oxygenation Survival Prediction (RESP) Score, Predicting Death for Severe ARDS on V­V ECMO (PRESERVE) Score, and 30-day survival. RESULTS: In our study cohort which enrolled 127 patients, overall 30-day survival was 54%. Median SOFA, SAPS II, APACHE II, RESP, and PRESERVE were 9, 36, 17, 1, and 4, respectively. The prognostic accuracy for all these scores (area under the receiver operating characteristic-AUROC) ranged between 0.548 and 0.605. CONCLUSIONS: The use of scores for the prediction of mortality cannot be recommended for treatment decisions in severe COVID-19 ARDS undergoing V-V ECMO; nevertheless, scoring results below or above a specific cut-off value may be considered as an additional tool in the evaluation of prognosis. Survival rates in this cohort of COVID-19 patients treated with V­V ECMO were slightly lower than those reported in non-COVID-19 ARDS patients treated with V-V ECMO.

Interleukine-6 in critically ill COVID-19 patients: A retrospective analysis.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) appeared in China in December 2019 and has spread around the world. High Interleukin-6 (IL-6) levels in COVID-19 patients suggest that a cytokine storm may play a major role in the pathophysiology and are considered as a relevant parameter in predicting most severe course of disease. The aim of this study was to assess repeated IL-6 levels in critically ill COVID-19 patients admitted to our Intensive Care Unit (ICU) and to evaluate their relationship with patient's severity and outcome. METHODS: We conducted a retrospective study on patients admitted to the ICU with a diagnosis of COVID-19 between March 10 (i.e. the date of the first admitted patients) and April 30, 2020. Demographic, clinical and laboratory data were collected at admission. On the day of IL-6 blood concentration measurement, we also collected results of D-Dimers, C-Reactive Protein, white blood cells and lymphocytes count, lactate dehydrogenase (LDH) and ferritin as well as microbiological samples, whenever present. RESULTS: Of a total of 65 patients with COVID-19 admitted to our ICU we included 41 patients with repeated measure of IL-6. There was a significant difference in IL-6 levels between survivors and non-survivors over time (p = 0.001); moreover, non survivors had a significantly higher IL-6 maximal value when compared to survivors (720 [349-2116] vs. 336 [195-646] pg/mL, p = 0.01). The IL-6 maximal value had a significant predictive value of ICU mortality (AUROC 0.73 [95% CI 0.57-0.89]; p = 0.01). CONCLUSIONS: Repeated measurements of IL-6 can help clinicians in identifying critically ill COVID-19 patients with the highest risk of poor prognosis.

Eosinopenia in COVID-19 Patients: A Retrospective Analysis.

Objectives: The aim of this study was to assess the diagnostic role of eosinophils count in COVID-19 patients. Methods: Retrospective analysis of patients admitted to our hospital with suspicion of COVID-19. Demographic, clinical and laboratory data were collected on admission. Eosinopenia was defined as eosinophils < 100 cells/mm3. The outcomes of this study were the association between eosinophils count on admission and positive real-time reverse transcription polymerase chain reaction (rRT-PCR) test and with suggestive chest computerized tomography (CT) of COVID-19 pneumonia. Results: A total of 174 patients was studied. Of those, 54% had positive rRT-PCR for SARS-CoV-2. A chest CT-scan was performed in 145 patients; 71% showed suggestive findings of COVID-19. Eosinophils on admission had a high predictive accuracy for positive rRT-PCR and suggestive chest CT-scan (area under the receiver operating characteristic-ROC curve, 0.84 (95% CIs 0.78-0.90) and 0.84 (95% CIs 0.77-0.91), respectively). Eosinopenia and high LDH were independent predictors of positive rRT-PCR, whereas eosinopenia, high body mass index and hypertension were predictors for suggestive CT-scan findings. Conclusions: Eosinopenia on admission could predict positive rRT-PCR test or suggestive chest CT-scan for COVID-19. This laboratory finding could help to identify patients at high-risk of COVID-19 in the setting where gold standard diagnostic methods are not available.

Unspecific post-mortem findings despite multiorgan viral spread in COVID-19 patients.

BACKGROUND: Post-mortem studies can provide important information for understanding new diseases and small autopsy case series have already reported different findings in COVID-19 patients. METHODS: We evaluated whether some specific post-mortem features are observed in these patients and if these changes are related to the presence of the virus in different organs. Complete macroscopic and microscopic autopsies were performed on different organs in 17 COVID-19 non-survivors. Presence of SARS-CoV-2 was evaluated with immunohistochemistry (IHC) in lung samples and with real-time reverse-transcription polymerase chain reaction (RT-PCR) test in the lung and other organs. RESULTS: Pulmonary findings revealed early-stage diffuse alveolar damage (DAD) in 15 out of 17 patients and microthrombi in small lung arteries in 11 patients. Late-stage DAD, atypical pneumocytes, and/or acute pneumonia were also observed. Four lung infarcts, two acute myocardial infarctions, and one ischemic enteritis were observed. There was no evidence of myocarditis, hepatitis, or encephalitis. Kidney evaluation revealed the presence of hemosiderin in tubules or pigmented casts in most patients. Spongiosis and vascular congestion were the most frequently encountered brain lesions. No specific SARS-CoV-2 lesions were observed in any organ. IHC revealed positive cells with a heterogeneous distribution in the lungs of 11 of the 17 (65%) patients; RT-PCR yielded a wide distribution of SARS-CoV-2 in different tissues, with 8 patients showing viral presence in all tested organs (i.e., lung, heart, spleen, liver, colon, kidney, and brain). CONCLUSIONS: In conclusion, autopsies revealed a great heterogeneity of COVID-19-associated organ injury and the remarkable absence of any specific viral lesions, even when RT-PCR identified the presence of the virus in many organs.

Higher Intensity Thromboprophylaxis Regimens and Pulmonary Embolism in Critically Ill Coronavirus Disease 2019 Patients.

OBJECTIVES: To assess the role of thromboprophylaxis regimens on the occurrence of pulmonary embolism in coronavirus disease 2019 patients. DESIGN: Retrospective analysis of prospectively collected data on coronavirus disease 2019 patients, included between March 10, and April 30, 2020. SETTING: ICU of an University Hospital in Belgium. PATIENTS AND INTERVENTIONS: Critically ill adult mechanically ventilated coronavirus disease 2019 patients were eligible if they underwent a CT pulmonary angiography, as part of the routine management in case of persistent hypoxemia or respiratory deterioration. The primary endpoint of this study was the occurrence of pulmonary embolism according to the use of standard thromboprophylaxis (i.e. subcutaneous enoxaparin 4,000 international units once daily) or high regimen thromboprophylaxis (i.e. subcutaneous enoxaparin 4,000 international units bid or therapeutic unfractioned heparin). MEASUREMENTS AND MAIN RESULTS: Of 49 mechanically ventilated coronavirus disease 2019, 40 underwent CT pulmonary angiography after a median of 7 days (4-8 d) since ICU admission and 12 days (9-16 d) days since the onset of symptoms. Thirteen patients (33%) were diagnosed of pulmonary embolism, which was bilateral in six patients and localized in the right lung in seven patients. D-dimers on the day of CT pulmonary angiography had a predictive accuracy of 0.90 (95% CIs: 0.78-1.00) for pulmonary embolism. The use of high-regimen thromboprophylaxis was associated with a lower occurrence of pulmonary embolism (2/18; 11%) than standard regimen (11/22, 50%-odds ratio 0.13 [0.02-0.69]; p = 0.02); this difference remained significant even after adjustment for confounders. Six patients with pulmonary embolism (46%) and 14 patients without pulmonary embolism (52%) died at ICU discharge (odds ratio 0.79 [0.24-3.26]; p = 0.99). CONCLUSIONS: In this study, one third of coronavirus disease 2019 mechanically ventilated patients have a pulmonary embolism visible on CT pulmonary angiography. High regimen thromboprophylaxis may decrease the occurrence of such complication.