Relationship between D-dimers and dead-space on disease severity and mortality in COVID-19 acute respiratory distress syndrome: A retrospective observational cohort study

Background Despite its diagnostic and prognostic importance, physiologic dead space fraction is not included in the current ARDS definition or severity classification. ARDS caused by COVID-19 (C-ARDS) is characterized by increased physiologic dead space fraction and hypoxemia. Our aim was to investigate the relationship between dead space indices, markers of inflammation, immunothrombosis, severity and intensive care unit (ICU) mortality. Results Retrospective data including demographics, gas exchange, ventilatory parameters, and respiratory mechanics in the first 24 h of invasive ventilation. Plasma concentrations of D-dimers and ferritin were not significantly different across C-ARDS severity categories. Weak relationships were found between D-dimers and VR (r = 0.07, p = 0.13), PETCO2/PaCO2 (r = −0.1, p = 0.02), or estimated dead space fraction (r = 0.019, p = 0.68). Age, PaO2/FiO2, pH, PETCO2/PaCO2 and ferritin, were independently associated with ICU mortality. We found no association between D-dimers or ferritin and any dead-space indices adjusting for PaO2/FiO2, days of ventilation, tidal volume, and respiratory system compliance. Conclusions We report no association between dead space and inflammatory markers in mechanically ventilated patients with C-ARDS. Our results support theories suggesting that multiple mechanisms, in addition to immunothrombosis, play a role in the pathophysiology of respiratory failure and degree of dead space in C-ARDS.

Hemorrhage, Disseminated Intravascular Coagulopathy, and Thrombosis Complications Among Critically Ill Patients with COVID-19: An International COVID-19 Critical Care Consortium Study.

OBJECTIVES: To determine the prevalence and outcomes associated with hemorrhage, disseminated intravascular coagulopathy, and thrombosis (HECTOR) complications in ICU patients with COVID-19. DESIGN: Prospective, observational study. SETTING: Two hundred twenty-nine ICUs across 32 countries. PATIENTS: Adult patients (≥ 16 yr) admitted to participating ICUs for severe COVID-19 from January 1, 2020, to December 31, 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: HECTOR complications occurred in 1,732 of 11,969 study eligible patients (14%). Acute thrombosis occurred in 1,249 patients (10%), including 712 (57%) with pulmonary embolism, 413 (33%) with myocardial ischemia, 93 (7.4%) with deep vein thrombosis, and 49 (3.9%) with ischemic strokes. Hemorrhagic complications were reported in 579 patients (4.8%), including 276 (48%) with gastrointestinal hemorrhage, 83 (14%) with hemorrhagic stroke, 77 (13%) with pulmonary hemorrhage, and 68 (12%) with hemorrhage associated with extracorporeal membrane oxygenation (ECMO) cannula site. Disseminated intravascular coagulation occurred in 11 patients (0.09%). Univariate analysis showed that diabetes, cardiac and kidney diseases, and ECMO use were risk factors for HECTOR. Among survivors, ICU stay was longer (median days 19 vs 12; p < 0.001) for patients with versus without HECTOR, but the hazard of ICU mortality was similar (hazard ratio [HR] 1.01; 95% CI 0.92-1.12; p = 0.784) overall, although this hazard was identified when non-ECMO patients were considered (HR 1.13; 95% CI 1.02-1.25; p = 0.015). Hemorrhagic complications were associated with an increased hazard of ICU mortality compared to patients without HECTOR complications (HR 1.26; 95% CI 1.09-1.45; p = 0.002), whereas thrombosis complications were associated with reduced hazard (HR 0.88; 95% CI 0.79-0.99, p = 0.03). CONCLUSIONS: HECTOR events are frequent complications of severe COVID-19 in ICU patients. Patients receiving ECMO are at particular risk of hemorrhagic complications. Hemorrhagic, but not thrombotic complications, are associated with increased ICU mortality.

Differences in clinical characteristics and quantitative lung CT features between vaccinated and not vaccinated hospitalized COVID-19 patients in Italy.

BACKGROUND: To evaluate the differences in the clinical characteristics and severity of lung impairment, assessed by quantitative lung CT scan, between vaccinated and non-vaccinated hospitalized patients with COVID-19; and to identify the variables with best prognostic prediction according to SARS-CoV-2 vaccination status. We recorded clinical, laboratory and quantitative lung CT scan data in 684 consecutive patients [580 (84.8%) vaccinated, and 104 (15.2%) non-vaccinated], admitted between January and December 2021. RESULTS: Vaccinated patients were significantly older 78 [69-84] vs 67 [53-79] years and with more comorbidities. Vaccinated and non-vaccinated patients had similar PaO2/FiO2 (300 [252-342] vs 307 [247-357] mmHg; respiratory rate 22 [8-26] vs 19 [18-26] bpm); total lung weight (918 [780-1069] vs 954 [802-1149] g), lung gas volume (2579 [1801-3628] vs 2370 [1675-3289] mL) and non-aerated tissue fraction (10 [7.3-16.0] vs 8.5 [6.0-14.1] %). The overall crude hospital mortality was similar between the vaccinated and non-vaccinated group (23.1% vs 21.2%). However, Cox regression analysis, adjusted for age, ethnicity, age unadjusted Charlson Comorbidity Index and calendar month of admission, showed a 40% reduction in hospital mortality in the vaccinated patients (HRadj = 0.60, 95%CI 0.38-0.95). CONCLUSIONS: Hospitalized vaccinated patients with COVID-19, although older and with more comorbidities, presented a similar impairment in gas exchange and lung CT scan compared to non-vaccinated patients, but were at a lower risk of mortality.

Mechanical Power Ratio and Respiratory Treatment Escalation in COVID-19 Pneumonia: A Secondary Analysis of a Prospectively Enrolled Cohort.

BACKGROUND: Under the hypothesis that mechanical power ratio could identify the spontaneously breathing patients with a higher risk of respiratory failure, this study assessed lung mechanics in nonintubated patients with COVID-19 pneumonia, aiming to (1) describe their characteristics; (2) compare lung mechanics between patients who received respiratory treatment escalation and those who did not; and (3) identify variables associated with the need for respiratory treatment escalation. METHODS: Secondary analysis of prospectively enrolled cohort involving 111 consecutive spontaneously breathing adults receiving continuous positive airway pressure, enrolled from September 2020 to December 2021. Lung mechanics and other previously reported predictive indices were calculated, as well as a novel variable: the mechanical power ratio (the ratio between the actual and the expected baseline mechanical power). Patients were grouped according to the outcome: (1) no-treatment escalation (patient supported in continuous positive airway pressure until improvement) and (2) treatment escalation (escalation of the respiratory support to noninvasive or invasive mechanical ventilation), and the association between lung mechanics/predictive scores and outcome was assessed. RESULTS: At day 1, patients undergoing treatment escalation had spontaneous tidal volume similar to those of patients who did not (7.1 ± 1.9 vs. 7.1 ± 1.4 ml/kgIBW; P = 0.990). In contrast, they showed higher respiratory rate (20 ± 5 vs. 18 ± 5 breaths/min; P = 0.028), minute ventilation (9.2 ± 3.0 vs. 7.9 ± 2.4 l/min; P = 0.011), tidal pleural pressure (8.1 ± 3.7 vs. 6.0 ± 3.1 cm H2O; P = 0.003), mechanical power ratio (2.4 ± 1.4 vs. 1.7 ± 1.5; P = 0.042), and lower partial pressure of alveolar oxygen/fractional inspired oxygen tension (174 ± 64 vs. 220 ± 95; P = 0.007). The mechanical power (area under the curve, 0.738; 95% CI, 0.636 to 0.839] P < 0.001), the mechanical power ratio (area under the curve, 0.734; 95% CI, 0.625 to 0.844; P < 0.001), and the pressure-rate index (area under the curve, 0.733; 95% CI, 0.631 to 0.835; P < 0.001) showed the highest areas under the curve. CONCLUSIONS: In this COVID-19 cohort, tidal volume was similar in patients undergoing treatment escalation and in patients who did not; mechanical power, its ratio, and pressure-rate index were the variables presenting the highest association with the clinical outcome.

Acute Improvements of Oxygenation with Cpap and Clinical Outcomes in Severe COVID-19 Pneumonia: A Multicenter, Retrospective Study.

It is not known if the degrees of improvement in oxygenation obtained by CPAP can predict clinical outcomes in patients with COVID-19 pneumonia. This was a retrospective study conducted on patients with severe COVID-19 pneumonia treated with CPAP in three University hospitals in Milan, Italy, from March 2020 to March 2021. Arterial gas analysis was obtained before and 1 h after starting CPAP. CPAP failure included either death in the respiratory units while on CPAP or the need for intubation. Two hundred and eleven patients (mean age 64 years, 74% males) were included. Baseline median PaO2, PaO2/FiO2 ratio (P/F), and the alveolar-arterial (A-a) O2 gradient were 68 (57−83) mmHg, 129 (91−179) mmHg and 310 (177−559) mmHg, respectively. Forty-two (19.9%) patients died in the respiratory units and 51 (24.2%) were intubated. After starting CPAP, PaO2/FiO2 increased by 57 (12−113; p < 0.001) mmHg, and (A-a) O2 was reduced by 68 (−25−250; p < 0.001) mmHg. A substantial overlap of PaO2, P/F, and A-a gradient at baseline and during CPAP was observed in CPAP failures and successes; CPAP-associated improvements in oxygenation in both groups were similar. In conclusion, CPAP-associated improvements in oxygenation do not predict clinical outcomes in patients with severe COVID-19 pneumonia.

Association of COVID-19 Vaccinations With Intensive Care Unit Admissions and Outcome of Critically Ill Patients With COVID-19 Pneumonia in Lombardy, Italy.

Importance: Data on the association of COVID-19 vaccination with intensive care unit (ICU) admission and outcomes of patients with SARS-CoV-2-related pneumonia are scarce. Objective: To evaluate whether COVID-19 vaccination is associated with preventing ICU admission for COVID-19 pneumonia and to compare baseline characteristics and outcomes of vaccinated and unvaccinated patients admitted to an ICU. Design, Setting, and Participants: This retrospective cohort study on regional data sets reports: (1) daily number of administered vaccines and (2) data of all consecutive patients admitted to an ICU in Lombardy, Italy, from August 1 to December 15, 2021 (Delta variant predominant). Vaccinated patients received either mRNA vaccines (BNT162b2 or mRNA-1273) or adenoviral vector vaccines (ChAdOx1-S or Ad26.COV2). Incident rate ratios (IRRs) were computed from August 1, 2021, to January 31, 2022; ICU and baseline characteristics and outcomes of vaccinated and unvaccinated patients admitted to an ICU were analyzed from August 1 to December 15, 2021. Exposures: COVID-19 vaccination status (no vaccination, mRNA vaccine, adenoviral vector vaccine). Main Outcomes and Measures: The incidence IRR of ICU admission was evaluated, comparing vaccinated people with unvaccinated, adjusted for age and sex. The baseline characteristics at ICU admission of vaccinated and unvaccinated patients were investigated. The association between vaccination status at ICU admission and mortality at ICU and hospital discharge were also studied, adjusting for possible confounders. Results: Among the 10 107 674 inhabitants of Lombardy, Italy, at the time of this study, the median [IQR] age was 48 [28-64] years and 5 154 914 (51.0%) were female. Of the 7 863 417 individuals who were vaccinated (median [IQR] age: 53 [33-68] years; 4 010 343 [51.4%] female), 6 251 417 (79.5%) received an mRNA vaccine, 550 439 (7.0%) received an adenoviral vector vaccine, and 1 061 561 (13.5%) received a mix of vaccines and 4 497 875 (57.2%) were boosted. Compared with unvaccinated people, IRR of individuals who received an mRNA vaccine within 120 days from the last dose was 0.03 (95% CI, 0.03-0.04; P < .001), whereas IRR of individuals who received an adenoviral vector vaccine after 120 days was 0.21 (95% CI, 0.19-0.24; P < .001). There were 553 patients admitted to an ICU for COVID-19 pneumonia during the study period: 139 patients (25.1%) were vaccinated and 414 (74.9%) were unvaccinated. Compared with unvaccinated patients, vaccinated patients were older (median [IQR]: 72 [66-76] vs 60 [51-69] years; P < .001), primarily male individuals (110 patients [79.1%] vs 252 patients [60.9%]; P < .001), with more comorbidities (median [IQR]: 2 [1-3] vs 0 [0-1] comorbidities; P < .001) and had higher ratio of arterial partial pressure of oxygen (Pao2) and fraction of inspiratory oxygen (FiO2) at ICU admission (median [IQR]: 138 [100-180] vs 120 [90-158] mm Hg; P = .007). Factors associated with ICU and hospital mortality were higher age, premorbid heart disease, lower Pao2/FiO2 at ICU admission, and female sex (this factor only for ICU mortality). ICU and hospital mortality were similar between vaccinated and unvaccinated patients. Conclusions and Relevance: In this cohort study, mRNA and adenoviral vector vaccines were associated with significantly lower risk of ICU admission for COVID-19 pneumonia. ICU and hospital mortality were not associated with vaccinated status. These findings suggest a substantial reduction of the risk of developing COVID-19-related severe acute respiratory failure requiring ICU admission among vaccinated people.

Level of Diffusion and Training of Lung Ultrasound during the COVID-19 Pandemic - A National Online Italian Survey (ITALUS) from the Lung Ultrasound Working Group of the Italian Society of Anesthesia, Analgesia, Resuscitation, and Intensive Care (SIAARTI).

PURPOSE: The goal of this survey was to describe the use and diffusion of lung ultrasound (LUS), the level of training received before and during the COVID-19 pandemic, and the clinical impact LUS has had on COVID-19 cases in intensive care units (ICU) from February 2020 to May 2020. MATERIALS AND METHODS: The Italian Lung Ultrasound Survey (ITALUS) was a nationwide online survey proposed to Italian anesthesiologists and intensive care physicians carried out after the first wave of the COVID-19 pandemic. It consisted of 27 questions, both quantitative and qualitative. RESULTS: 807 responded to the survey. The median previous LUS experience was 3 years (IQR 1.0-6.0). 473 (60.9 %) reported having attended at least one training course on LUS before the COVID-19 pandemic. 519 (73.9 %) reported knowing how to use the LUS score. 404 (52 %) reported being able to use LUS without any supervision. 479 (68.2 %) said that LUS influenced their clinical decision-making, mostly with respect to patient monitoring. During the pandemic, the median of patients daily evaluated with LUS increased 3-fold (p < 0.001), daily use of general LUS increased from 10.4 % to 28.9 % (p < 0.001), and the daily use of LUS score in particular increased from 1.6 % to 9.0 % (p < 0.001). CONCLUSION: This survey showed that LUS was already extensively used during the first wave of the COVID-19 pandemic by anesthesiologists and intensive care physicians in Italy, and then its adoption increased further. Residency programs are already progressively implementing LUS teaching. However, 76.7 % of the sample did not undertake any LUS certification.

Risk Factors and Mortality in Elderly ARDS COVID-19 Compared to Patients without COVID-19.

During the last few decades, due to the increase in elderly patients among the general population, the number of patients aged over 80 years admitted in intensive care significantly incremented [...].

Positive end-expiratory pressure in COVID-19 acute respiratory distress syndrome: the heterogeneous effects.

BACKGROUND: We hypothesized that as CARDS may present different pathophysiological features than classic ARDS, the application of high levels of end-expiratory pressure is questionable. Our first aim was to investigate the effects of 5-15 cmH2O of PEEP on partitioned respiratory mechanics, gas exchange and dead space; secondly, we investigated whether respiratory system compliance and severity of hypoxemia could affect the response to PEEP on partitioned respiratory mechanics, gas exchange and dead space, dividing the population according to the median value of respiratory system compliance and oxygenation. Thirdly, we explored the effects of an additional PEEP selected according to the Empirical PEEP-FiO2 table of the EPVent-2 study on partitioned respiratory mechanics and gas exchange in a subgroup of patients. METHODS: Sixty-one paralyzed mechanically ventilated patients with a confirmed diagnosis of SARS-CoV-2 were enrolled (age 60 [54-67] years, PaO2/FiO2 113 [79-158] mmHg and PEEP 10 [10-10] cmH2O). Keeping constant tidal volume, respiratory rate and oxygen fraction, two PEEP levels (5 and 15 cmH2O) were selected. In a subgroup of patients an additional PEEP level was applied according to an Empirical PEEP-FiO2 table (empirical PEEP). At each PEEP level gas exchange, partitioned lung mechanics and hemodynamic were collected. RESULTS: At 15 cmH2O of PEEP the lung elastance, lung stress and mechanical power were higher compared to 5 cmH2O. The PaO2/FiO2, arterial carbon dioxide and ventilatory ratio increased at 15 cmH2O of PEEP. The arterial-venous oxygen difference and central venous saturation were higher at 15 cmH2O of PEEP. Both the mechanics and gas exchange variables significantly increased although with high heterogeneity. By increasing the PEEP from 5 to 15 cmH2O, the changes in partitioned respiratory mechanics and mechanical power were not related to hypoxemia or respiratory compliance. The empirical PEEP was 18 ± 1 cmH2O. The empirical PEEP significantly increased the PaO2/FiO2 but also driving pressure, lung elastance, lung stress and mechanical power compared to 15 cmH2O of PEEP. CONCLUSIONS: In COVID-19 ARDS during the early phase the effects of raising PEEP are highly variable and cannot easily be predicted by respiratory system characteristics, because of the heterogeneity of the disease.

Early short course of neuromuscular blocking agents in patients with COVID-19 ARDS: a propensity score analysis.

BACKGROUND: The role of neuromuscular blocking agents (NMBAs) in coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS) is not fully elucidated. Therefore, we aimed to investigate in COVID-19 patients with moderate-to-severe ARDS the impact of early use of NMBAs on 90-day mortality, through propensity score (PS) matching analysis. METHODS: We analyzed a convenience sample of patients with COVID-19 and moderate-to-severe ARDS, admitted to 244 intensive care units within the COVID-19 Critical Care Consortium, from February 1, 2020, through October 31, 2021. Patients undergoing at least 2 days and up to 3 consecutive days of NMBAs (NMBA treatment), within 48 h from commencement of IMV were compared with subjects who did not receive NMBAs or only upon commencement of IMV (control). The primary objective in the PS-matched cohort was comparison between groups in 90-day in-hospital mortality, assessed through Cox proportional hazard modeling. Secondary objectives were comparisons in the numbers of ventilator-free days (VFD) between day 1 and day 28 and between day 1 and 90 through competing risk regression. RESULTS: Data from 1953 patients were included. After propensity score matching, 210 cases from each group were well matched. In the PS-matched cohort, mean (± SD) age was 60.3 ± 13.2 years and 296 (70.5%) were male and the most common comorbidities were hypertension (56.9%), obesity (41.1%), and diabetes (30.0%). The unadjusted hazard ratio (HR) for death at 90 days in the NMBA treatment vs control group was 1.12 (95% CI 0.79, 1.59, p = 0.534). After adjustment for smoking habit and critical therapeutic covariates, the HR was 1.07 (95% CI 0.72, 1.61, p = 0.729). At 28 days, VFD were 16 (IQR 0-25) and 25 (IQR 7-26) in the NMBA treatment and control groups, respectively (sub-hazard ratio 0.82, 95% CI 0.67, 1.00, p = 0.055). At 90 days, VFD were 77 (IQR 0-87) and 87 (IQR 0-88) (sub-hazard ratio 0.86 (95% CI 0.69, 1.07; p = 0.177). CONCLUSIONS: In patients with COVID-19 and moderate-to-severe ARDS, short course of NMBA treatment, applied early, did not significantly improve 90-day mortality and VFD. In the absence of definitive data from clinical trials, NMBAs should be indicated cautiously in this setting.

Acid-Base Disorders in COVID-19 Patients with Acute Respiratory Distress Syndrome.

Our aim was to investigate the distribution of acid-base disorders in patients with COVID-19 ARDS using both the Henderson-Hasselbalch and Stewart's approach and to explore if hypoxemia can influence acid-base disorders. COVID-19 ARDS patients, within the first 48 h of the need for a non-invasive respiratory support, were retrospectively enrolled. Respiratory support was provided by helmet continuous positive airway pressure (CPAP) or by non-invasive ventilation. One hundred and four patients were enrolled, 84% treated with CPAP and 16% with non-invasive ventilation. Using the Henderson-Hasselbalch approach, 40% and 32% of patients presented respiratory and metabolic alkalosis, respectively; 13% did not present acid-base disorders. Using Stewart's approach, 43% and 33% had a respiratory and metabolic alkalosis, respectively; 12% of patients had a mixed disorder characterized by normal pH with a lower SID. The severe hypoxemic and moderate hypoxemic group presented similar frequencies of respiratory and metabolic alkalosis. The most frequent acid-base disorders were respiratory and metabolic alkalosis using both the Henderson-Hasselbalch and Stewart's approach. Stewart's approach detected mixed disorders with a normal pH probably generated by the combined effect of strong ions and weak acids. The impairment of oxygenation did not affect acid-base disorders.

Evidence of SARS-CoV-2 in nasal brushings and olfactory mucosa biopsies of COVID-19 patients.

The aim of the present study is to detect the presence of SARS-CoV-2 of patients affected by COVID-19 in olfactory mucosa (OM), sampled with nasal brushing (NB) and biopsy, and to assess whether a non-invasive procedure, such as NB, might be used as a large-scale procedure for demonstrating SARS-CoV-2 presence in olfactory neuroepithelium. Nasal brushings obtained from all the COVID-19 patients resulted positive to SARS-CoV-2 immunocytochemistry while controls were negative. Double immunofluorescence showed that SARS-CoV-2 positive cells included supporting cells as well as olfactory neurons and basal cells. OM biopsies showed an uneven distribution of SARS-CoV-2 positivity along the olfactory neuroepithelium, while OM from controls were negative. SARS-CoV-2 was distinctively found in sustentacular cells, olfactory neurons, and basal cells, supporting what was observed in NB. Ultrastructural analysis of OM biopsies showed SARS-CoV-2 viral particles in the cytoplasm of sustentacular cells. This study shows the presence of SARS-CoV-2 at the level of the olfactory neuroepithelium in patients affected by COVID-19. For the first time, we used NB as a rapid non-invasive tool for assessing a potential neuroinvasion by SARS-CoV-2 infection.

Real World Estimate of Vaccination Protection in Individuals Hospitalized for COVID-19.

Whether vaccination confers a protective effect against progression after hospital admission for COVID-19 remains to be elucidated. Observational study including all the patients admitted to San Paolo Hospital in Milan for COVID-19 in 2021. Previous vaccination was categorized as: none, one dose, full vaccination (two or three doses >14 days before symptoms onset). Data were collected at hospital admission, including demographic and clinical variables, age-unadjusted Charlson Comorbidity index (CCI). The highest intensity of ventilation during hospitalization was registered. The endpoints were in-hospital death (primary) and mechanical ventilation/death (secondary). Survival analysis was conducted by means of Kaplan-Meier curves and Cox regression models. Effect measure modification by age was formally tested. We included 956 patients: 151 (16%) fully vaccinated (18 also third dose), 62 (7%) one dose vaccinated, 743 (78%) unvaccinated. People fully vaccinated were older and suffering from more comorbidities than unvaccinated. By 28 days, the risk of death was of 35.9% (95%CI: 30.1-41.7) in unvaccinated, 41.5% (24.5-58.5) in one dose and 28.4% (18.2-38.5) in fully vaccinated (p = 0.63). After controlling for age, ethnicity, CCI and month of admission, fully vaccinated participants showed a risk reduction of 50% for both in-hospital death, AHR 0.50 (95%CI: 0.30-0.84) and for mechanical ventilation or death, AHR 0.49 (95%CI: 0.35-0.69) compared to unvaccinated, regardless of age (interaction p > 0.56). Fully vaccinated individuals in whom vaccine failed to keep them out of hospital, appeared to be protected against critical disease or death when compared to non-vaccinated. These data support universal COVID-19 vaccination.

Prone Position in COVID-19 and -COVID-19 Acute Respiratory Distress Syndrome: An International Multicenter Observational Comparative Study.

OBJECTIVES: Prone position is used in acute respiratory distress syndrome and in coronavirus disease 2019 acute respiratory distress syndrome. However, it is unclear how responders may be identified and whether an oxygenation response improves outcome. The objective of this study was to quantify the response to prone position, describe the differences between coronavirus disease 2019 acute respiratory distress syndrome and acute respiratory distress syndrome, and explore variables associated with survival. DESIGN: Retrospective, observational, multicenter, international cohort study. SETTING: Seven ICUs in Italy, United Kingdom, and France. PATIENTS: Three hundred seventy-six adults (220 coronavirus disease 2019 acute respiratory distress syndrome and 156 acute respiratory distress syndrome). INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Preproning, a greater proportion of coronavirus disease 2019 acute respiratory distress syndrome patients had severe disease (53% vs 40%), worse Pao2/Fio2 (13.0 kPa [interquartile range, 10.5-15.5 kPa] vs 14.1 kPa [interquartile range, 10.5-18.6 kPa]; p = 0.017) but greater compliance (38 mL/cm H2O [interquartile range, 27-53 mL/cm H2O] vs 31 mL/cm H2O [interquartile range, 21-37 mL/cm H2O]; p < 0.001). Patients with coronavirus disease 2019 acute respiratory distress syndrome had a longer median time from intubation to prone position (2.0 d [interquartile range, 0.7-5.0 d] vs 1.0 d [interquartile range, 0.5-2.9 d]; p = 0.03). The proportion of responders, defined by an increase in Pao2/Fio2 greater than or equal to 2.67 kPa (20 mm Hg), upon proning, was similar between acute respiratory distress syndrome and coronavirus disease 2019 acute respiratory distress syndrome (79% vs 76%; p = 0.5). Responders had earlier prone position (1.4 d [interquartile range, 0.7-4.2 d] vs 2.5 d [interquartile range, 0.8-6.2 d]; p = 0.06)]. Prone position less than 24 hours from intubation achieved greater improvement in oxygenation (11 kPa [interquartile range, 4-21 kPa] vs 7 kPa [interquartile range, 2-13 kPa]; p = 0.002). The variables independently associated with the "responder" category were Pao2/Fio2 preproning (odds ratio, 0.89 kPa-1 [95% CI, 0.85-0.93 kPa-1]; p < 0.001) and interval between intubation and proning (odds ratio, 0.94 d-1 [95% CI, 0.89-0.99 d-1]; p = 0.019). The overall mortality was 45%, with no significant difference observed between acute respiratory distress syndrome and coronavirus disease 2019 acute respiratory distress syndrome. Variables independently associated with mortality included age (odds ratio, 1.03 yr-1 [95% CI, 1.01-1.05 yr-1]; p < 0.001); interval between hospital admission and proning (odds ratio, 1.04 d-1 [95% CI, 1.002-1.084 d-1]; p = 0.047); and change in Pao2/Fio2 on proning (odds ratio, 0.97 kPa-1 [95% CI, 0.95-0.99 kPa-1]; p = 0.002). CONCLUSIONS: Prone position, particularly when delivered early, achieved a significant oxygenation response in ~80% of coronavirus disease 2019 acute respiratory distress syndrome, similar to acute respiratory distress syndrome. This response was independently associated with improved survival.

Putative Role of the Lung-Brain Axis in the Pathogenesis of COVID-19-Associated Respiratory Failure: A Systematic Review.

The emergence of SARS-CoV-2 and its related disease caused by coronavirus (COVID-19) has posed a huge threat to the global population, with millions of deaths and the creation of enormous social and healthcare pressure. Several studies have shown that besides respiratory illness, other organs may be damaged as well, including the heart, kidneys, and brain. Current evidence reports a high frequency of neurological manifestations in COVID-19, with significant prognostic implications. Importantly, emerging literature is showing that the virus may spread to the central nervous system through neuronal routes, hitting the brainstem and cardiorespiratory centers, potentially exacerbating the respiratory illness. In this systematic review, we searched public databases for all available evidence and discuss current clinical and pre-clinical data on the relationship between the lung and brain during COVID-19. Acknowledging the involvement of these primordial brain areas in the pathogenesis of the disease may fuel research on the topic and allow the development of new therapeutic strategies.