Echocardiographic detection of transpulmonary bubble transit during coronavirus-2019 disease (COVID-19)

Background: Transpulmonary bubble transit (TPBT) detected with contrast echocardiography is reported as a sign of intrapulmonary arteriovenous shunt. However, its pathological meaning is not clear during coronavirus-2019 disease (COVID-19) related acute respiratory distress syndrome (ARDS). Our aim was to determine the prevalence and clinical significance of TPBT detection during COVID-19 related ARDS. Methods: We carried out a prospective observational study performed in a high complexity intensive care unit from Argentina. Patients with COVID-19 related ARDS underwent transthoracic echocardiography with saline contrast. Moderate-to-large TPBT was defined as right-to-left passage of at least twelve bubbles to left chambers after at least three cardiac cycles and complete opacification of the right atrium. Results: We analyzed the results of 28 patients (24 men and 4 women). Seventy-five percent of the patients received invasive mechanical ventilation. Moderate-to-large TPBT was detected in 1 patient (3.5%). Among the 27 patients without significant TPBT, 23 had no TPBT and 4 had a minor TPBT. TPBT was not associated with invasive mechanical ventilation requirement (p = 0.5737) nor in-hospital mortality (p = 1). Conclusions: TPBT was not associated with severe hypoxemia or invasive mechanical ventilation requirement, although more studies are needed to further clarify its contributing role in COVID-19 hypoxemia. © 2023 Asociación Colombiana de Medicina Crítica y Cuidado lntensivo

Prolonged Versus Standard Prone Position in Covid-19 Ventilated Patients: A Quasi-Experimental Study

INTRODUCTION: Acute respiratory distress syndrome (ARDS) related to COVID-19 increased the number of patients requiring prone position ventilation (PPV). The ProSEVA PPV strategy of daily reproning is resource intensive because each complete PPV cycle takes half an hour of work from 4 experienced operators. Therefore the Standard PPV was extended until 24 to 48 hours. In 2021 Douglas et al. propose the Prolonged PPV strategy for COVID-19 ARDS, returning to the supine position only when the patient has stable gas exchange (Fio2< 60% with PEEP< 10cmH2O). This strategy was secure, but they did not compare the clinical outcomes of the Prolonged against the Standard PPV. In this study, we compare the number of PPV cycles and pressure wounds (PWs) in COVID-19 patients with Standard PPV vs. Prolonged PPV. METHOD(S): Quasi-experimental before-and-after study. We included ventilated patients with PPV indication (criteria from the ProSEVA Trial). Between October 1, 2020, to April 30, 2021, patients with indication of PPV received the standard PPV (24 to 48 hs), and patients hospitalized between May 1, 2021, to October 1, 2021, were treated with the Prolonged PPV. For the primary outcome (number of PPV cycles), we compare the proportion of patients with more than 2 PPV cycles in each group. As a sensitivity analysis, we performed a Fine and Gray regression adjusting by confounders, considering death as a competing event, two PPV cycles as the event, and censoring patients with one PPV cycle at ICU discharge. RESULT(S): We included 64 patients in the Standard PPV group and 16 in the Prolonged PPV group. No differences were observed in the number of PPV cycles between groups (patients with more than one cycle: 42.2% [n=27] vs. 62.5% [n=10];p=0.18). These observations were robust to the sensitivity analysis (the adjusted sHR to have two PPV cycles for the Prolonged PPV group was 1.31 [CI95% 0.63-2.71;p=0.46]). Patients in Prolonged PPV had 2.96 (IQR1.98-3.42) days in PPV vs. 1.98 (IQR1.38-2.94) in the Standard PPV (p=0.03). Chest and abdominal PWs were more frequently in the Prolonged PPV group (chest wounds: 5 patients [31.5%] vs 5 [7.8%];p=0.024 - abdominal: 3 [18.8%] vs 2 [3.12%];p=0.02). CONCLUSION(S): The Prolonged PPV increases the time in PPV and the PPV-associated PWs but does not reduce the total PPV cycles.

Covid-19 Vaccine Protection against Mortality in Patients with Oxygen: A Multicontinental Study

INTRODUCTION: The COVID-19 vaccines have effectiveness above 90% for avoiding hospitalization. However, 5% of vaccinated patients require hospitalization with a mortality ratio between 15% to 24%, similar to the one reported for unvaccinated hospitalized patients. These vaccinated patients belong to the most sensitive groups with a high comorbidity burden. The similarity in the mortality ratio between vaccinated and unvaccinated patients has been used to make claims against the vaccine's efficacy. A thoughtful analysis, taking into account the comorbidities of each group, on how vaccination protects patients with moderate or severe illness, is missing. METHOD(S): We perform a multi-continental retrospective cohort study in 111 hospitals in Spain and 37 in Argentina. We included hospitalized patients who received oxygen therapy older than 18 years with COVID-19. To assess the relation between COVID-19 vaccine status and death, we performed a logistic regression adjusting by confounders. Also, as a sensitivity analysis, we perform a propensityscore matching. Additionally, we studied the Population Attributable Risk (PAR). RESULT(S): Between January 2020 and May 2022, we included 21,479 patients, 717 (3 3%) were vaccinated. Hospitalized vaccinated patients with oxygen therapy had a higher proportion of comorbidities. The overall mortality in vaccinated patients was 20 9%, and 19 5% in unvaccinated patients. The crude Odds Ratio was 1 07 (IC95% 0 89-1 29;p=0 41), while the adjusted was 0 73 (IC95% 0 56-0 95;p=0 02) in the complete case analysis (6,352 patients) and 0 77 (CI 95% 0 54-0 97;p=0 02) in the complete dataset after multiple imputations. These observations were robust to the sensitivity analysis. The adjusted PAR reduction was 4 3% (95%CI 1%-5%). Therefore, as the death proportion in unvaccinated patients was 19 6% (95%CI 19%-20 1%), if they were vaccinated the expected death proportion would have been 15 3% (95%CI 12 9%-18%;p< 0 01). CONCLUSION(S): Even with the high protection of the COVID-19 vaccine, patients with a high burden of comorbidities will be hospitalized in future pandemic waves. In this study, we observed that the COVID-19 vaccines significantly reduce the probability of death even when lung inflammation has already been initiated, with moderate or severe COVID-19 disease.

Multicenter validation of Early Warning Scores for detection of clinical deterioration in COVID-19 hospitalized patients.

OBJECTIVE: Investigate the predictive value of NEWS2, NEWS-C, and COVID-19 Severity Index for predicting intensive care unit (ICU) transfer in the next 24h. DESIGN: Retrospective multicenter study. SETTING: Two third-level hospitals in Argentina. PATIENTS: All adult patients with confirmed COVID-19, admitted on general wards, excluding patients with non-intubated orders. INTERVENTIONS: Patients were divided between those who were admitted to ICU and non-admitted. We calculated the three scores for each day of hospitalization. VARIABLES: We evaluate the calibration and discrimination of the three scores for the outcome ICU admission within 24, 48h, and at hospital admission. RESULTS: We evaluate 13,768 days of hospitalizations on general medical wards of 1318 patients. Among these, 126 (9.5%) were transferred to ICU. The AUROC of NEWS2 was 0.73 (95%CI 0.68-0.78) 24h before ICU admission, and 0.52 (95%CI 0.47-0.57) at hospital admission. The AUROC of NEWS-C was 0.73 (95%CI 0.68-0.78) and 0.52 (95%CI 0.47-0.57) respectively, and the AUROC of COVID-19 Severity Index was 0.80 (95%CI 0.77-0.84) and 0.61 (95%CI 0.58-0.66) respectively. COVID-19 Severity Index presented better calibration than NEWS2 and NEWS-C. CONCLUSION: COVID-19 Severity index has better calibration and discrimination than NEWS2 and NEWS-C to predict ICU transfer during hospitalization.

Multicenter validation of Early Warning Scores for detection of clinical deterioration in COVID-19 hospitalized patients Validación multicéntrica de Sistemas de Alerta Temprana para la detección precoz de deterioro clínico en pacientes hospitalizados por COVID-19

Objective Investigate the predictive value of NEWS2, NEWS-C, and COVID-19 Severity Index for predicting intensive care unit (ICU) transfer in the next 24 h. Design Retrospective multicenter study. Setting Two third-level hospitals in Argentina. Patients All adult patients with confirmed COVID-19, admitted on general wards, excluding patients with non-intubated orders. Interventions Patients were divided between those who were admitted to ICU and non-admitted. We calculated the three scores for each day of hospitalization. Variables We evaluate the calibration and discrimination of the three scores for the outcome ICU admission within 24, 48 h, and at hospital admission. Results We evaluate 13,768 days of hospitalizations on general medical wards of 1318 patients. Among these, 126 (9.5%) were transferred to ICU. The AUROC of NEWS2 was 0.73 (95%CI 0.68–0.78) 24 h before ICU admission, and 0.52 (95%CI 0.47–0.57) at hospital admission. The AUROC of NEWS-C was 0.73 (95%CI 0.68–0.78) and 0.52 (95%CI 0.47–0.57) respectively, and the AUROC of COVID-19 Severity Index was 0.80 (95%CI 0.77–0.84) and 0.61 (95%CI 0.58–0.66) respectively. COVID-19 Severity Index presented better calibration than NEWS2 and NEWS-C. Conclusion COVID-19 Severity index has better calibration and discrimination than NEWS2 and NEWS-C to predict ICU transfer during hospitalization.

CHARACTERISTICS OF ACUTE KIDNEY INJURY IN ADULT PATIENTS WITH SEVERE COVID-19

We conducted a retrospective cohort study to report the clinical characteristics, incidence and outcomes of patients with severe COVID-19 with acute kidney injury (AKI). One-hundred and sixtytwo intensive care unit (ICU) admitted patients in a tertiary level hospital in the city of Buenos Aires with COVID-19 diagnosis were included. We hypothesized that COVID-19 related AKI would develop in the period of more severe hypoxemia as an early event and late AKI would be more probably related to intensive care unit complications. For this purpose, we divided subjects into two groups: those with early AKI and late AKI, before and after day 14 from symptom onset, respectively. A stepwise multivariate analysis was conducted to find possible AKI predictors. AKI incidence was 43.2% (n = 70) of the total patients admitted into ICU with severe COVID-19, 11.1% (n = 18) required renal replacement therapy. In-hospital mortality was higher (58.6%) for the AKI group. AKI occurred on a median time of 10 (IQR 5.5-17.5) days from symptom onset. A history of hypertension or heart failure, age and invasive mechanical ventilation (IMV) requirement were identified as risk factors. Late AKI (n = 25, 35.7%) was associated with sepsis and nephrotoxic exposure, whereas early AKI occurred closer to the timing of IMV initiation and was more likely to have an unknown origin. In conclusion, AKI is frequent among critically ill patients with severe COVID-19 and it is associated with higher in-hospital mortality.

Design and development of an early warning score for COVID-19 hospitalized patients

Pandemics pose a major challenge for public health preparedness, requiring a coordinated inter- national response and the development of solid containment plans. Early and accurate identification of high-risk patients in the course of the current COVID-19 pandemic is vital for planning and making proper use of available resources. The purpose of this study was to identify the key variables that account for worse outcomes to create a predictive model that could be used effectively for triage. Through literature review, 44 variables that could be linked to an unfavorable course of COVID-19 disease were obtained, including clinical, laboratory, and X-ray variables. These were used for a 2-round modified Delphi processing with 14 experts to select a final list of variables with the greatest predictive power for the construction of a scoring system, leading to the creation of a new scoring system: the COVID-19 Severity Index. The analysis of the area under the curve for the COVID-19 Severity Index was 0.94 to predict the need for ICU admission in the following 24 hours against 0.80 for NEWS-2. Additionally, the digital medical record of the Hospital Italiano de Buenos Aires was electronically set for an automatic calculation and constant update of the COVID-19 Severity Index. Specifically designed for the current COVID-19 pandemic, COVID-19 Severity Index could be used as a reliable tool for strategic planning, organization, and administration of resources by easily identifying hospitalized patients with a greater need of intensive care.

Transient lupus anticoagulant presence in COVID-19 pneumonia, a probably epiphenomenon

Background : High prevalence of Lupus anticoagulant (LA) has been reported in COVID-19 infection. Aims : To determine the presence and the evolution of LA in COVID-19 pneumonia en the first 10 days at Intensive Care Unit (UCI). Methods : Prospective observational cohort study: Consecutive adult COVID-19 patients admitted to ICU. Exclusion criteria: age > 80 years, anticoagulation, tocilizumab, convalescent plasma transfusion, thrombophilia, pregnancy and cancer.Blood samples on day 1, 5 and 10 from UCI admission. Studies: PT, APTT, silica clotting time [HemosILSCT, Instrumentation laboratory(IL)], diluted Russell viper venom time HemosILDRVVT(IL) and STADRVVT(STAGO Diagnostic). Screening. Mixing with normal pooled plasma (NP) and confirmatory tests should be above their cur off points to be consider LA+. Biomarkers: D Dimer(DD), Reactive Protein C high sentitivity(cRP-H), Ferritina, LDH and interleukin 6(IL 6). Results : Patients included: 23, age 57 y (IQR52-71), 70% male, 15 required mechanical ventilation(MV).Twelve(52.1%) had LA+ by HemosILDRVVT in at least one time point, 3 in 3, 1 in 2(T5,10) and 8 in one(7/8 T1, 1/8 T5);4/5 patients with hospital discharge before T10 presented LA+ only at T1. LA prevalence was lower with STADRVVT(Table 1). SCT was negative in all samples. CRP-H, IL6 and Ferritin were higher in LA+, particularly at T5 and T10(Table 2). We cannot exclude CRP interference in DRVVT many samples had CRP > 126 (maximum concentration tested in vitro on NP). Patients received prophylactic enoxaparin, samples were taken at through, antiXa = 0.08 (0.04-0.12)U/mL, ruling out interference. LA+ was not associated with death ( n = 4) or VM requirement. Only one LA-patient developed pulmonary thromboembolism after leaving ICU. Conclusions : LA presence was demonstrated in this cohort of COVID-19 Pneumonia patients. Its presence was transient during the short period evaluated, LA was diagnosed through DRVVT with differences between regents. LA presence was associated with inflammatory biomarkers but not with MV requirement or death. These results confirm that LA is probably an epiphenomena.

Hypercoagulable rotational thromboelastometry naheptem profile is related to mechanical ventilation requirementamong critically ill COVID-19 patients

Background : Hypercoagulability and pulmonary microvascular thrombosis has been related to COVID-19 hypoxemia. Rotational thromboelastometry (RT) could identify the procoagulant state. Aims : -To evaluate maximum clot firmness(MCF) and other RT parameters among COVID-19 patients in intensive care unit(ICU) compared to healthy controls(HC) -To compare them according to mechanical ventilation (MV) requirement Methods : Prospective observational cohort study (August-November 2020). ICU cohort: All adult patients admitted due to COVID-19. HC cohort: healthy volunteers. Coagulation profile was evaluated by RT NaHEPTEM assay in ROTEM Delta at day 1 (T1), 5 (T5) and 10 (T10) from ICU admission. D-Dimer and Fibrinogen were also evaluated. Results : Twenty three COVID-19 patients (under prophylactic dose enoxaparin) and 19 HC were included. MCF was statistically higher in ICU patients vs HC at admission (T1) and further increasing at T5. (Table 1) Distribution of NaHEPTEM parameters, DD and Fibrinogen in samples from ICU patients under MV or not are shown in Figure 1. ICU patients under MV compared to non-MV presented higher levels of fibrinogen from T1 to T10, DD and MCF at T5,and shorter clotting formation time (CFT), higher maximum velocity (MaxV) and 5 min Amplitude (A5) at T1. Maximum Lysis (ML) was significantly lower at T5 and T10 compared to T1, P = 0.003 and P = 0.008, respectively, but not associated with MV. (TABLE1). COVID-19 patients discharged from hospital before T10 ( n = 5) presented at T5 significant lower values of DD, Fibrinogen and RT MaxV compared to patients with longer UCI stay. Conclusions : NaHEPTEM assay could detect hypercoagulability among COVID-19 critically ill patients. Velocity parameters(CFT, MaxV) and A5 seem to be further altered in patients that required MV at early stages after ICU admission, probably reflecting increased thrombin generation. MCF and DD were higher at T5 post ICU admission in patients under MV. ML decreased along to study period without association to MV and no difference to HC. Further studies are needed to evaluate its clinical usefulness.