Long-Term Evolution of Activities of Daily Life (ADLs) in Critically Ill COVID-19 Patients, a Case Series

Background: The most common long-term symptoms of critically ill COVID-19 patients are fatigue, dyspnea and mental confusion. Adequate monitoring of long-term morbidity, mainly analyzing the activities of daily life (ADLs), allows better patient management after hospital discharge. The aim was to report long-term ADL evolution in critically ill COVID-19 patients admitted to a COVID-19 center in Lugano (Switzerland). Methods: A retrospective analysis on consecutive patients discharged alive from ICU with COVID-19 ARDS was performed based on a follow-up one year after hospital discharge;ADLs were assessed through the Barthel index (BI) and the Karnofsky Performance Status (KPS) scale. The primary objective was to assess differences in ADLs at hospital discharge (acute ADLs) and one-year follow-up (chronic ADLs). The secondary objective was to explore any correlations between ADLs and multiple measures at admission and during the ICU stay. Results: A total of 38 consecutive patients were admitted to the ICU;a t-test analysis between acute and chronic ADLs through BI showed a significant improvement at one year post discharge (t = −5.211, p < 0.0001);similarly, every single task of BI showed the same results (p < 0.0001 for each task of BI). The mean KPS was 86.47 (SD 20.9) at hospital discharge and 99.6 at 1 year post discharge (p = 0.02). Thirteen (34%) patients deceased during the first 28 days in the ICU;no patient died after hospital discharge. Conclusions: Based on BI and KPS, patients reached complete functional recovery of ADLs one year after critical COVID-19.

Long-Term Evolution of Activities of Daily Life (ADLs) in Critically Ill COVID-19 Patients, a Case Series.

BACKGROUND: The most common long-term symptoms of critically ill COVID-19 patients are fatigue, dyspnea and mental confusion. Adequate monitoring of long-term morbidity, mainly analyzing the activities of daily life (ADLs), allows better patient management after hospital discharge. The aim was to report long-term ADL evolution in critically ill COVID-19 patients admitted to a COVID-19 center in Lugano (Switzerland). METHODS: A retrospective analysis on consecutive patients discharged alive from ICU with COVID-19 ARDS was performed based on a follow-up one year after hospital discharge; ADLs were assessed through the Barthel index (BI) and the Karnofsky Performance Status (KPS) scale. The primary objective was to assess differences in ADLs at hospital discharge (acute ADLs) and one-year follow-up (chronic ADLs). The secondary objective was to explore any correlations between ADLs and multiple measures at admission and during the ICU stay. RESULTS: A total of 38 consecutive patients were admitted to the ICU; a t-test analysis between acute and chronic ADLs through BI showed a significant improvement at one year post discharge (t = -5.211, p < 0.0001); similarly, every single task of BI showed the same results (p < 0.0001 for each task of BI). The mean KPS was 86.47 (SD 20.9) at hospital discharge and 99.6 at 1 year post discharge (p = 0.02). Thirteen (34%) patients deceased during the first 28 days in the ICU; no patient died after hospital discharge. CONCLUSIONS: Based on BI and KPS, patients reached complete functional recovery of ADLs one year after critical COVID-19.

Reply to Böning et al. Comment on "Ceruti et al. Temporal Changes in the Oxyhemoglobin Dissociation Curve of Critically Ill COVID-19 Patients. J. Clin. Med. 2022, 11, 788".

We would like to thank Böning et al. for all the important issues raised in the present commentary [...].

Nasogastric tube in mechanical ventilated patients: ETCO2 and pH measuring to confirm correct placement. A pilot study.

INTRODUCTION: Nasogastric tube (NGT) placement is a procedure commonly performed in mechanically ventilated (MV) patients. Chest X-Ray is the diagnostic gold-standard to confirm its correct placement, with the downsides of requiring MV patients' mobilization and of intrinsic actinic risk. Other potential methods to confirm NGT placement have shown lower accuracy compared to chest X-ray; end-tidal CO2 (ETCO2) and pH analysis have already been singularly investigated as an alternative to the gold standard. Aim of this study was to determine threshold values in ETCO2 and pH measurement at which correct NGT positioning can be confirmed with the highest accuracy. MATERIALS & METHODS: This was a prospective, multicenter, observational trial; a continuous cohort of eligible patients was allocated with site into two arms. Patients underwent general anesthesia, orotracheal intubation and MV; in the first and second group we respectively assessed the difference between tracheal and esophageal ETCO2 and between esophageal and gastric pH values. RESULTS: From November 2020 to March 2021, 85 consecutive patients were enrolled: 40 in the ETCO2 group and 45 in the pH group. The ETCO2 ROC analysis for predicting NGT tracheal misplacement demonstrated an optimal ETCO2 cutoff value of 25.5 mmHg, with both sensitivity and specificity reaching 1.0 (AUC 1.0, p < 0.001). The pH ROC analysis for predicting NGT correct gastric placement resulted in an optimal pH cutoff value of 4.25, with mild diagnostic accuracy (AUC 0.79, p < 0.001). DISCUSSION: In patients receiving MV, ETCO2 and pH measurements respectively identified incorrect and correct NGT placement, allowing the identification of threshold values potentially able to improve correct NGT positioning. TRIAL REGISTRATION: NCT03934515 (www.clinicaltrials.gov).

Dynamics of disease characteristics and clinical management of critically ill COVID-19 patients over the time course of the pandemic: an analysis of the prospective, international, multicentre RISC-19-ICU registry.

BACKGROUND: It remains elusive how the characteristics, the course of disease, the clinical management and the outcomes of critically ill COVID-19 patients admitted to intensive care units (ICU) worldwide have changed over the course of the pandemic. METHODS: Prospective, observational registry constituted by 90 ICUs across 22 countries worldwide including patients with a laboratory-confirmed, critical presentation of COVID-19 requiring advanced organ support. Hierarchical, generalized linear mixed-effect models accounting for hospital and country variability were employed to analyse the continuous evolution of the studied variables over the pandemic. RESULTS: Four thousand forty-one patients were included from March 2020 to September 2021. Over this period, the age of the admitted patients (62 [95% CI 60-63] years vs 64 [62-66] years, p < 0.001) and the severity of organ dysfunction at ICU admission decreased (Sequential Organ Failure Assessment 8.2 [7.6-9.0] vs 5.8 [5.3-6.4], p < 0.001) and increased, while more female patients (26 [23-29]% vs 41 [35-48]%, p < 0.001) were admitted. The time span between symptom onset and hospitalization as well as ICU admission became longer later in the pandemic (6.7 [6.2-7.2| days vs 9.7 [8.9-10.5] days, p < 0.001). The PaO2/FiO2 at admission was lower (132 [123-141] mmHg vs 101 [91-113] mmHg, p < 0.001) but showed faster improvements over the initial 5 days of ICU stay in late 2021 compared to early 2020 (34 [20-48] mmHg vs 70 [41-100] mmHg, p = 0.05). The number of patients treated with steroids and tocilizumab increased, while the use of therapeutic anticoagulation presented an inverse U-shaped behaviour over the course of the pandemic. The proportion of patients treated with high-flow oxygen (5 [4-7]% vs 20 [14-29], p < 0.001) and non-invasive mechanical ventilation (14 [11-18]% vs 24 [17-33]%, p < 0.001) throughout the pandemic increased concomitant to a decrease in invasive mechanical ventilation (82 [76-86]% vs 74 [64-82]%, p < 0.001). The ICU mortality (23 [19-26]% vs 17 [12-25]%, p < 0.001) and length of stay (14 [13-16] days vs 11 [10-13] days, p < 0.001) decreased over 19 months of the pandemic. CONCLUSION: Characteristics and disease course of critically ill COVID-19 patients have continuously evolved, concomitant to the clinical management, throughout the pandemic leading to a younger, less severely ill ICU population with distinctly different clinical, pulmonary and inflammatory presentations than at the onset of the pandemic.

Temporal Changes in the Oxyhemoglobin Dissociation Curve of Critically Ill COVID-19 Patients.

Critical COVID-19 is a life-threatening disease characterized by severe hypoxemia with complex pathophysiological mechanisms that are not yet completely understood. A pathological shift in the oxyhemoglobin curve (ODC) was previously described through the analysis of p50, intended as the oxygen tension at which hemoglobin is saturated by oxygen at 50%. The aim of this study was to analyze Hb-O2 affinity features over time in a cohort of critically ill COVID-19 patients, through the analysis of ODC p50 behavior. A retrospective analysis was performed; through multiple arterial blood gas (ABG) analyses, each p50 was calculated and normalized according to PaCO2, pH and temperature; patients' p50 evolution over time was reported, comparing the first 3 days (early p50s) with the last 3 days (late p50s) of ICU stay. A total of 3514 ABG analyses of 32 consecutive patients were analyzed. The majority of patients presented a left shift over time (p = 0.03). A difference between early p50s and late p50s was found (20.63 ± 2.1 vs. 18.68 ± 3.3 mmHg, p = 0.03); median p50 of deceased patients showed more right shifts than those of alive patients (24.1 vs. 18.45 mmHg, p = 0.01). One-way ANOVA revealed a p50 variance greater in the early p50s (σ2 = 8.6) than in the late p50s (σ2 = 3.84), associated with a reduction over time (p < 0.001). Comparing the Hb-O2 affinity in critically ill COVID-19 patients between ICU admission and ICU discharge, a temporal shift in the ODC was observed.

Admission criteria in critically ill COVID-19 patients: A physiology-based approach.

INTRODUCTION: The COVID-19 pandemic required careful management of intensive care unit (ICU) admissions, to reduce ICU overload while facing limitations in resources. We implemented a standardized, physiology-based, ICU admission criteria and analyzed the mortality rate of patients refused from the ICU. MATERIALS AND METHODS: In this retrospective observational study, COVID-19 patients proposed for ICU admission were consecutively analyzed; Do-Not-Resuscitate patients were excluded. Patients presenting an oxygen peripheral saturation (SpO2) lower than 85% and/or dyspnea and/or mental confusion resulted eligible for ICU admission; patients not presenting these criteria remained in the ward with an intensive monitoring protocol. Primary outcome was both groups' survival rate. Secondary outcome was a sub analysis correlating SpO2 cutoff with ICU admission. RESULTS: From March 2020 to January 2021, 1623 patients were admitted to our Center; 208 DNR patients were excluded; 97 patients were evaluated. The ICU-admitted group (n = 63) mortality rate resulted 15.9% at 28 days and 27% at 40 days; the ICU-refused group (n = 34) mortality rate resulted 0% at both intervals (p < 0.001). With a SpO2 cut-off of 85%, a significant correlation was found (p = 0.009), but with a 92% a cut-off there was no correlation with ICU admission (p = 0.26). A similar correlation was also found with dyspnea (p = 0.0002). CONCLUSION: In COVID-19 patients, standardized ICU admission criteria appeared to safely reduce ICU overload. In the absence of dyspnea and/or confusion, a SpO2 cutoff up to 85% for ICU admission was not burdened by negative outcomes. In a pandemic context, the SpO2 cutoff of 92%, as a threshold for ICU admission, needs critical re-evaluation.

Dysphagic disorder in a cohort of COVID-19 patients: Evaluation and evolution.

BACKGROUND: COVID-19 is a multisystem disease complicated by respiratory failure requiring sustanined mechanical ventilation (MV). Prolongued oro-tracheal intubation is associated to an increased risk of dysphagia and bronchial aspiration. Purpose of this study was to investigate swallowing disorders in critically ill COVID-19 patients. MATERIAL AND METHODS: This was a retrospective study analysing a consecutive cohort of COVID-19 patients admitted to the Intensive Care Unit (ICU) of our hospital. Data concerning dysphagia were collected according to the Gugging Swallowing Screen (GUSS) and related to demographic characteristics, clinical data, ICU Length-Of-Stay (LOS) and MV parameters. RESULTS: From March 2 to April 30, 2020, 31 consecutive critically ill COVID-19 patients admitted to ICU were evaluated by speech and language therapists (SLT). Twenty-five of them were on MV (61% through endotracheal tube and 19% through tracheostomy); median MV length was 11 days. Seventeen (54.8%) patients presented dysphagia; a correlation was found between first GUSS severity stratification and MV days (p < 0.001), ICU LOS (p < 0.001), age (p = 0.03) and tracheostomy (p = 0.042). No other correlations were found. At 16 days, 90% of patients had fully recovered; a significant improvement was registered especially during the first week (p < 0.001). CONCLUSION: Compared to non-COVID-19 patiens, a higher rate of dysphagia was reported in COVID-19 patients, with a more rapid and complete recovery. A systematic early SLT evaluation of COVID-19 patients on MV may thus be useful to prevent dysphagia-related complications.

Multidisciplinary team approach in critically ill COVID-19 patients reduced pronation-related complications rate: A retrospective cohort study.

BACKGROUND: In the pandemic scenario, critically ill COVID-19 patients' management presented an increased workload for Intensive Care Unit (ICU) nursing staff, particularly during pronation maneuvers, with high risk of complications. In this contest, some authors described an increase in complications incidence after pronation. An ICU Pronation Team (IPT) was implemented to support this maneuver. MATERIAL AND METHODS: Retrospective analysis was conducted on consecutive critically ill COVID-19 patients in COVID-19 Center in southern Switzerland, between March and April 2020. Aim of the study was to determine rates and characteristics of pronation-related complications managed by IPT according to standard protocols. RESULTS: Forty-two patients undergoing mechanical ventilation (MV) were enrolled; 296 prone/supine positioning were performed, with 3.52 cycles/patient. All patients were equipped with arterial line, central venous catheter, urinary catheter, 28 (66%) endotracheal tube, 8 (19%), tracheostomy, 6 (14%) dialysis catheter, 3 (7%) abdominal drainage and 8 (19%) femoral thermodilution catheter; mean BMI was 28.3 kg/m2. One (0.3%) major complication was observed, while fourteen (33.3%) patients developed minor complications (pressure injuries). ICU length-of-stay and MV days correlated with both incidence (p = 0.029 and p = 0.015 respectively) and number (p = 0.001 and p = 0.001 respectively) of pressure sores (n = 27). Propensity matching score analysis did not show any protective factor of pronation regarding pressure injuries (p = 0.448). No other significant correlation was found. CONCLUSION: Multidisciplinary healthcare professional management can reduce most severe complication related to pronation in critical care setting. Rather than from pronation, the persistent high rate of minor complications appeared to be related to disease severity.

Broad betacoronavirus neutralization by a stem helix-specific human antibody.

The spillovers of betacoronaviruses in humans and the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants highlight the need for broad coronavirus countermeasures. We describe five monoclonal antibodies (mAbs) cross-reacting with the stem helix of multiple betacoronavirus spike glycoproteins isolated from COVID-19 convalescent individuals. Using structural and functional studies, we show that the mAb with the greatest breadth (S2P6) neutralizes pseudotyped viruses from three different subgenera through the inhibition of membrane fusion, and we delineate the molecular basis for its cross-reactivity. S2P6 reduces viral burden in hamsters challenged with SARS-CoV-2 through viral neutralization and Fc-mediated effector functions. Stem helix antibodies are rare, oftentimes of narrow specificity, and can acquire neutralization breadth through somatic mutations. These data provide a framework for structure-guided design of pan-betacoronavirus vaccines eliciting broad protection.

Low PEEP Mechanical Ventilation and PaO2/FiO2 Ratio Evolution in COVID-19 Patients.

Invasive mechanical ventilation (IMV) is the standard treatment in critically ill COVID-19 patients with acute severe respiratory distress syndrome (ARDS). When IMV setting is extremely aggressive, especially through the application of high positive-end-expiratory respiration (PEEP) values, lung damage can occur. Until today, in COVID-19 patients, two types of ARDS were identified (L- and H-type); for the L-type, a lower PEEP strategy was supposed to be preferred, but data are still missing. The aim of this study was to evaluate if a clinical management with lower PEEP values in critically ill L-type COVID-19 patients was safe and efficient in comparison to usual standard of care. A retrospective analysis was conducted on consecutive patients with COVID-19 ARDS admitted to the ICU and treated with IMV. Patients were treated with a lower PEEP strategy adapted to BMI: PEEP 10 cmH2O if BMI < 30 kg m-2, PEEP 12 cmH2O if BMI 30-50 kg m-2, PEEP 15 cmH2O if BMI > 50 kg m-2. Primary endpoint was the PaO2/FiO2 ratio evolution during the first 3 IMV days; secondary endpoints were to analyze ICU length of stay (LOS) and IMV length. From March 2 to January 15, 2021, 79 patients underwent IMV. Average applied PEEP was 11 ± 2.9 cmH2O for BMI < 30 kg m-2 and 16 ± 3.18 cmH2O for BMI > 30 kg m-2. During the first 24 h of IMV, patients' PaO2/FiO2 ratio presented an improvement (p<0.001; CI 99%) that continued daily up to 72 h (p<0.001; CI 99%). Median ICU LOS was 15 days (10-28); median duration of IMV was 12 days (8-26). The ICU mortality rate was 31.6%. Lower PEEP strategy treatment in L-type COVID-19 ARDS resulted in a PaO2/FiO2 ratio persistent daily improvement during the first 72 h of IMV. A lower PEEP strategy could be beneficial in the first phase of ARDS in critically ill COVID-19 patients.

Implications of early respiratory support strategies on disease progression in critical COVID-19: a matched subanalysis of the prospective RISC-19-ICU cohort.

BACKGROUND: Uncertainty about the optimal respiratory support strategies in critically ill COVID-19 patients is widespread. While the risks and benefits of noninvasive techniques versus early invasive mechanical ventilation (IMV) are intensely debated, actual evidence is lacking. We sought to assess the risks and benefits of different respiratory support strategies, employed in intensive care units during the first months of the COVID-19 pandemic on intubation and intensive care unit (ICU) mortality rates. METHODS: Subanalysis of a prospective, multinational registry of critically ill COVID-19 patients. Patients were subclassified into standard oxygen therapy ≥10 L/min (SOT), high-flow oxygen therapy (HFNC), noninvasive positive-pressure ventilation (NIV), and early IMV, according to the respiratory support strategy employed at the day of admission to ICU. Propensity score matching was performed to ensure comparability between groups. RESULTS: Initially, 1421 patients were assessed for possible study inclusion. Of these, 351 patients (85 SOT, 87 HFNC, 87 NIV, and 92 IMV) remained eligible for full analysis after propensity score matching. 55% of patients initially receiving noninvasive respiratory support required IMV. The intubation rate was lower in patients initially ventilated with HFNC and NIV compared to those who received SOT (SOT: 64%, HFNC: 52%, NIV: 49%, p = 0.025). Compared to the other respiratory support strategies, NIV was associated with a higher overall ICU mortality (SOT: 18%, HFNC: 20%, NIV: 37%, IMV: 25%, p = 0.016). CONCLUSION: In this cohort of critically ill patients with COVID-19, a trial of HFNC appeared to be the most balanced initial respiratory support strategy, given the reduced intubation rate and comparable ICU mortality rate. Nonetheless, considering the uncertainty and stress associated with the COVID-19 pandemic, SOT and early IMV represented safe initial respiratory support strategies. The presented findings, in agreement with classic ARDS literature, suggest that NIV should be avoided whenever possible due to the elevated ICU mortality risk.