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SARS-CoV-2 infection induces a humoral immune response, producing virus-specific antibodies such as IgM, IgG, and IgA. IgA antibodies are present at mucosal sites, protecting against respiratory and other mucosal infections, including SARS-CoV-2, by neutralizing viruses or impeding attachment to epithelial cells. Since SARS-CoV-2 spreads through the nasopharynx, the specific IgAs of SARS-CoV-2 are produced quickly after infection, effectively contributing to virus neutralization. Dimeric IgA has been reported to be 10 to 15 times more potent than its equivalent IgG, suggesting that this isotype may be particularly interesting in developing new monoclonal antibodies and/or new vaccines efficiently neutralizing the virus at the mucosal sites. It is still unclear whether IgA antibodies in BAL might play a role in the disease course and if their presence may have a prognostic significance. However, a harmful effect on diseases with high IgA titers has been reported. This study evaluated mucosal-specific IgA and IgG profiles in BAL of patients with COVID-19 acute respiratory failure admitted to the ICU. We included 57 patients (41 males and 16 females), admitted to the ICU of the University of Foggia. We used a commercially available ELISA assay to evaluate the presence of SARS-CoV-2 IgG and IgA antibodies in plasma and BAL of the 57 hospitalized patients with severe COVID-19 respiratory failure. However, 40/57 BAL and plasma from infected patients were available for the ELISA test; the remaining specimens were unsuitable. IgG and IgA antibodies against SARS-CoV-2 were detectable in 37 (92.5%) and 40 (100%) plasma specimens, respectively. IgG antibodies were found in a single sample, while IgAs were detected in 19 of 40 BAL samples analyzed. Correlations between these parameters and patient outcomes reveal a signature associated with survival. Interestingly, a statistically significant inverse correlation was found between the mortality rate and the presence of IgA to SARS-CoV-2 in BAL specimens. None of the 19 patients with a positive IgA died, compared to 7 out of 12 patients with a negative IgA-BAL (p: <0.0004). Despite being limited in size, this study suggests a significant protective effect of mucosal immunity in COVID-19 patients, even in advanced disease stages, and a role of IgA in the defense against the virus, as well as the possible use of effective vaccines and therapeutic strategies based on IgA antibodies. [ABSTRACT FROM AUTHOR]

Author(s): Annemijn H. Jonkman [sup.1] [sup.2] [sup.3] , Michela Rauseo [sup.1] [sup.2] , Guillaume Carteaux [sup.4] [sup.5] [sup.6] , Irene Telias [sup.1] [sup.2] , Michael C. Sklar [sup.1] [sup.2] , [...], Proportional modes of ventilation assist the patient by adapting to his/her effort, which contrasts with all other modes. The two proportional modes are referred to as neurally adjusted ventilatory assist (NAVA) and proportional assist ventilation with load-adjustable gain factors (PAV+): they deliver inspiratory assist in proportion to the patient&apos;s effort, and hence directly respond to changes in ventilatory needs. Due to their working principles, NAVA and PAV+ have the ability to provide self-adjusted lung and diaphragm-protective ventilation. As these proportional modes differ from &apos;classical&apos; modes such as pressure support ventilation (PSV), setting the inspiratory assist level is often puzzling for clinicians at the bedside as it is not based on usual parameters such as tidal volumes and PaCO.sub.2 targets. This paper provides an in-depth overview of the working principles of NAVA and PAV+ and the physiological differences with PSV. Understanding these differences is fundamental for applying any assisted mode at the bedside. We review different methods for setting inspiratory assist during NAVA and PAV+, and (future) indices for monitoring of patient effort. Last, differences with automated modes are mentioned.

Background: Both general anesthesia and pneumoperitoneum insufflation during abdominal laparoscopic surgery can lead to atelectasis and impairment in oxygenation. Setting an appropriate level of external PEEP could reduce the occurrence of atelectasis and induce an improvement in gas exchange. However, in clinical practice, it is common to use a fixed PEEP level (i.e., 5 cmH2O), irrespective of the dynamic respiratory mechanics. We hypothesized setting a PEEP level guided by EIT in order to obtain an improvement in oxygenation and respiratory system compliance in lung-healthy patients than can benefit a personalized approach. Methods: Twelve consecutive patients scheduled for abdominal laparoscopic surgery were enrolled in this prospective study. The EIT Timpel Enlight 1800 was applied to each patient and a dedicated pneumotachograph and a spirometer flow sensor, integrated with EIT, constantly recorded respiratory mechanics. Gas exchange, respiratory mechanics and hemodynamics were recorded at five time points: T0, baseline; T1, after induction; T2, after pneumoperitoneum insufflation; T3, after a recruitment maneuver; and T4, at the end of surgery after desufflation. Results: A titrated mean PEEP of 8 cmH2O applied after a recruitment maneuver was successfully associated with the "best" compliance (58.4 ± 5.43 mL/cmH2O), with a low percentage of collapse (10%), an acceptable level of hyperdistention (0.02%). Pneumoperitoneum insufflation worsened respiratory system compliance, plateau pressure, and driving pressure, which significantly improved after the application of the recruitment maneuver and appropriate PEEP. PaO2 increased from 78.1 ± 9.49 mmHg at T0 to 188 ± 66.7 mmHg at T4 (p < 0.01). Other respiratory parameters remained stable after abdominal desufflation. Hemodynamic parameters remained unchanged throughout the study. Conclusions: EIT, used as a non-invasive intra-operative monitor, enables the rapid assessment of lung volume and regional ventilation changes in patients undergoing laparoscopic surgery and helps to identify the "optimal" PEEP level in the operating theatre, improving ventilation strategies. [ABSTRACT FROM AUTHOR]

Muscle wasting (sarcopenia) is one of the hallmarks of critical illness. Patients admitted to intensive care unit develop sarcopenia through increased protein catabolism, a decrease in protein syntheses, or both. Among the factors known to promote wasting are chronic inflammation and cytokine imbalance, insulin resistance, hypermetabolism, and malnutrition. Moreover, muscle wasting, known to develop in chronic kidney disease patients, is a harmful consequence of numerous complications associated with deteriorated renal function. Plenty of published data suggest that serum creatinine (SCr) reflects increased kidney damage and is also related to body weight. Based on the concept that urea and creatinine are nitrogenous end products of metabolism, the urea:creatinine ratio (UCR) could be applied but with limited clinical usability in case of kidney damage, hypovolemia, excessive, or protein intake, where UCR can be high and independent of catabolism. Recent data suggest that the sarcopenia index should be considered an alternative to serum creatinine. It is more reliable in estimating muscle mass than SCr. However, the optimal biomarker of catabolism is still an unresolved issue. The SCr is not a promising biomarker for renal function and muscle mass based on the influence of several factors. The present review highlights recent findings on the limits of SCr as a surrogate marker of renal function and the assessment modalities of nutritional status and muscle mass measurements. [ABSTRACT FROM AUTHOR]

Am J Respir Crit Care Med 2020; 201:178-187 15 Mauri T, Spinelli E, Scotti E, et al: Potential for lung recruitment and ventilation-perfusion mismatch in patients with the acute respiratory distress syndrome from coronavirus disease 2019. Camporota et al ([6]) tackle on this point by comparing C-ARDS versus ARDS and their findings do underline that C-ARDS is not fully superimposable to ARDS. In this issue of Critical Care Medicine, Camporota et al ([6]) present a retrospective, observational study conducted on 376 adult patients admitted to ICU with ARDS, mechanically ventilated and made undergo PP: 220 had COVID-19-related ARDS and 156 patients ARDS from other causes. [Extracted from the article]

Rationale: Response to positive end-expiratory pressure (PEEP) in acute respiratory distress syndrome depends on recruitability. We propose a bedside approach to estimate recruitability accounting for the presence of complete airway closure.Objectives: To validate a single-breath method for measuring recruited volume and test whether it differentiates patients with different responses to PEEP.Methods: Patients with acute respiratory distress syndrome were ventilated at 15 and 5 cm H2O of PEEP. Multiple pressure-volume curves were compared with a single-breath technique. Abruptly releasing PEEP (from 15 to 5 cm H2O) increases expired volume: the difference between this volume and the volume predicted by compliance at low PEEP (or above airway opening pressure) estimated the recruited volume by PEEP. This recruited volume divided by the effective pressure change gave the compliance of the recruited lung; the ratio of this compliance to the compliance at low PEEP gave the recruitment-to-inflation ratio. Response to PEEP was compared between high and low recruiters based on this ratio.Measurements and Main Results: Forty-five patients were enrolled. Four patients had airway closure higher than high PEEP, and thus recruitment could not be assessed. In others, recruited volume measured by the experimental and the reference methods were strongly correlated (R2 = 0.798; P < 0.0001) with small bias (-21 ml). The recruitment-to-inflation ratio (median, 0.5; range, 0-2.0) correlated with both oxygenation at low PEEP and the oxygenation response; at PEEP 15, high recruiters had better oxygenation (P = 0.004), whereas low recruiters experienced lower systolic arterial pressure (P = 0.008).Conclusions: A single-breath method quantifies recruited volume. The recruitment-to-inflation ratio might help to characterize lung recruitability at the bedside.Clinical trial registered with www.clinicaltrials.gov (NCT02457741). [ABSTRACT FROM AUTHOR]

Mechanical ventilation is a life-saving technology, but it can also inadvertently induce lung injury and increase morbidity and mortality. Currently, there is no easy method of assessing the impact that ventilator settings have on the degree of lung inssflation. Computed tomography (CT), the gold standard for visually monitoring lung function, can provide detailed regional information of the lung. Unfortunately, it necessitates moving critically ill patients to a special diagnostic room and involves exposure to radiation. A technique introduced in the 1980s, electrical impedance tomography (EIT) can non-invasively provide similar monitoring of lung function. However, while CT provides information on the air content, EIT monitors ventilation-related changes of lung volume and changes of end expiratory lung volume (EELV). Over the past several decades, EIT has moved from the research lab to commercially available devices that are used at the bedside. Being complementary to well-established radiological techniques and conventional pulmonary monitoring, EIT can be used to continuously visualize the lung function at the bedside and to instantly assess the effects of therapeutic maneuvers on regional ventilation distribution. EIT provides a means of visualizing the regional distribution of ventilation and changes of lung volume. This ability is particularly useful when therapy changes are intended to achieve a more homogenous gas distribution in mechanically ventilated patients. Besides the unique information provided by EIT, its convenience and safety contribute to the increasing perception expressed by various authors that EIT has the potential to be used as a valuable tool for optimizing PEEP and other ventilator settings, either in the operative room and in the intensive care unit. The effects of various therapeutic interventions and applications on ventilation distribution have already been assessed with the help of EIT, and this document gives an overview of the literature that has been published in this context., (© 2022. The Author(s).)

Background: The authors tested the hypothesis that during laparoscopic surgery, Trendelenburg position and pneumoperitoneum may worsen chest wall elastance, concomitantly decreasing transpulmonary pressure, and that a protective ventilator strategy applied after pneumoperitoneum induction, by increasing transpulmonary pressure, would result in alveolar recruitment and improvement in respiratory mechanics and gas exchange., Methods: In 29 consecutive patients, a recruiting maneuver followed by positive end-expiratory pressure 5 cm H(2)O maintained until the end of surgery was applied after pneumoperitoneum induction. Respiratory mechanics, gas exchange, blood pressure, and cardiac index were measured before (T(BSL)) and after pneumoperitoneum with zero positive end-expiratory pressure (T(preOLS)), after recruitment with positive end-expiratory pressure (T(postOLS)), and after peritoneum desufflation with positive end-expiratory pressure (T(end))., Results: Esophageal pressure was used for partitioning respiratory mechanics between lung and chest wall (data are mean ± SD): on T(preOLS), chest wall elastance (E(cw)) and elastance of the lung (E(L)) increased (8.2 ± 0.9 vs. 6.2 ± 1.2 cm H(2)O/L, respectively, on T(BSL); P = 0.00016; and 11.69 ± 1.68 vs. 9.61 ± 1.52 cm H(2)O/L on T(BSL); P = 0.0007). On T(postOLS), both chest wall elastance and E(L) decreased (5.2 ± 1.2 and 8.62 ± 1.03 cm H(2)O/L, respectively; P = 0.00015 vs. T(preOLS)), and Pao(2)/inspiratory oxygen fraction improved (491 ± 107 vs. 425 ± 97 on T(preOLS); P = 0.008) remaining stable thereafter. Recruited volume (the difference in lung volume for the same static airway pressure) was 194 ± 80 ml. Pplat(RS) remained stable while inspiratory transpulmonary pressure increased (11.65 + 1.37 cm H(2)O vs. 9.21 + 2.03 on T(preOLS); P = 0.007). All respiratory mechanics parameters remained stable after abdominal desufflation. Hemodynamic parameters remained stable throughout the study., Conclusions: In patients submitted to laparoscopic surgery in Trendelenburg position, an open lung strategy applied after pneumoperitoneum induction increased transpulmonary pressure and led to alveolar recruitment and improvement of E(cw) and gas exchange.