Extracorporeal membrane oxygenation aggravates platelet glycoprotein V shedding and δ-granule deficiency in COVID-19-associated acute respiratory distress syndrome.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a lifesaving therapy in patients with acute respiratory distress syndrome (ARDS). Hemostatic complications are frequently observed in patients on ECMO and limit the success of this therapy. Platelets are key mediators of hemostasis enabling activation, aggregation, and thrombus formation by coming in contact with exposed matrix proteins via their surface receptors such as glycoprotein (GP) VI or GPIb/V/IX. Recent research has elucidated a regulatory role of the GPV subunit. The cleaved soluble GPV (sGPV) ectodomain was identified to spatiotemporally control fibrin formation through complex formation with thrombin. OBJECTIVES: We aimed to decipher the impact of ECMO on platelet phenotype and function, including the role of GPV and plasmatic sGPV. METHODS: We recruited 36 patients with ARDS in the wake of COVID-19 pneumonia and performed a longitudinal comparison of platelet phenotype and function in non-ECMO (n = 23) vs ECMO (n = 13) compared with those of healthy controls. Patients were assessed at up to 3 time points (t1 = days 1-3; t2 = days 4-6; and t3 = days 7-14 after cannulation/study inclusion). RESULTS: Agonist-induced platelet activation was assessed by flow cytometry and revealed decreased GPIIb/IIIa activation and α-granule release in all ARDS patients. During ECMO treatment, agonist-induced δ-granule release continuously decreased, which was independently confirmed by electron microscopy and was associated with a prolonged in vitro bleeding time. GPV expression on the platelet surface markedly decreased in ECMO patients compared with that in non-ECMO patients. Plasma sGPV levels were increased in ECMO patients and were associated with poor outcome. CONCLUSION: Our data demonstrate an ECMO-intrinsic platelet δ-granule deficiency and hemostatic dysfunction beyond the underlying ARDS.

Association of preclinical blood glucose with hospitalization rate and in-hospital mortality: A single-center retrospective cohort study.

Objective: Critical illness is often accompanied by elevated blood glucose, which generally correlates with increased morbidity and mortality. Prehospital blood glucose (PBG) level might be a useful and easy-to-perform tool for risk assessment in emergency medicine. This retrospective single-center cohort study was designed to analyze the association of prehospital glucose measurements with hospitalization rate and in-hospital mortality. Methods: Records of 970 patients admitted to a university hospital by an emergency physician were analyzed. Patients with a PBG ≥140 mg/dL (G1, n = 394, equal to 7.8 mmol/L) were compared with patients with a PBG <140 mg/dL (G2, n = 576). Multivariable logistic regression models were used to correct for age, prediagnosed diabetes, and sex. Results: Five hundred thirty-four patients (55%) were hospitalized. In comparison to normoglycemic patients, hyperglycemic patients were more likely to be hospitalized with an adjusted odds ratio (OR) of 1.48 (95% confidence interval [CI] 1.11-1.97), more likely to be admitted to the intensive care unit (ICU) with an adjusted OR of 1.74 (95% CI 1.31-2.31) and more likely to die in the hospital with an adjusted OR of 1.84 (95% CI 0.96-3.53). Hospitalized hyperglycemic patients had a median length of stay of 6.0 days (interquartile range [IQR] 8.0) compared to 3.0 days (IQR 6.0) in the normoglycemic group (P < 0.001). In the subgroup analysis of cases without known diabetes, patients with PBG ≥140 mg/dL were more likely to be hospitalized with an adjusted OR of 1.49 (95% CI 1.10-2.03) and more likely to be admitted to ICU/intermediate care with an adjusted OR of 1.80 (95% CI 1.32-2.45), compared to normoglycemic patients. Conclusion: Elevated PBG ≥140 mg/dL was associated with a higher hospitalization risk, a longer length of stay, and a higher mortality risk and may therefore be included in risk assessment scores.

Modelling variations of emergency attendances using data on community mobility, climate and air pollution.

Air pollution is associated with morbidity and mortality worldwide. We investigated the impact of improved air quality during the economic lockdown during the SARS-Cov2 pandemic on emergency room (ER) admissions in Germany. Weekly aggregated clinical data from 33 hospitals were collected in 2019 and 2020. Hourly concentrations of nitrogen and sulfur dioxide (NO2, SO2), carbon and nitrogen monoxide (CO, NO), ozone (O3) and particulate matter (PM10, PM2.5) measured by ground stations and meteorological data (ERA5) were selected from a 30 km radius around the corresponding ED. Mobility was assessed using aggregated cell phone data. A linear stepwise multiple regression model was used to predict ER admissions. The average weekly emergency numbers vary from 200 to over 1600 cases (total n = 2,216,217). The mean maximum decrease in caseload was 5 standard deviations. With the enforcement of the shutdown in March, the mobility index dropped by almost 40%. Of all air pollutants, NO2 has the strongest correlation with ER visits when averaged across all departments. Using a linear stepwise multiple regression model, 63% of the variation in ER visits is explained by the mobility index, but still 6% of the variation is explained by air quality and climate change.

[Analysis of the weaning process in intensive care patients with regard to documentation and transfer to further treatment units]. / Analyse des Weaningprozesses bei Intensivpatienten im Hinblick auf Dokumentation und Verlegung in weiterbehandelnde Einheiten.

BACKGROUND AND OBJECTIVES: Weaning from ventilators is not always finished in the primary intensive care unit (ICU) setting. Transfer to other treatment facilities is a sensitive stage in the treatment and rehabilitation of the weaning patient. The aim of the present study was to investigate transition management and interhospital transfer of weaning patients, with special emphasis on documentation quality. METHODS: A retrospective data analysis of one year (2018) in two ICUs of a university hospital was performed. All ventilated patients with the following tracer diagnoses were included: chronic obstructive pulmonary disease (COPD), asthma, patients with multiple injuries, pneumonia, sepsis, acute respiratory distress syndrome (ARDS), and cardiac arrest (ventilation > 24 h). RESULTS: A total of 750 patients were included in the study (median age 64 [IQR 52.8-76]; 32% female). In all, 48 (6.4%) patients were not weaned at the time of transfer (especially sepsis and ARDS). Routine documentation was sufficient for the sections "spontaneous breathing trial", "assessment of readiness to wean" and "presumed weanability" to adequately assess the parameters of the German S2k guideline "prolonged weaning". Predominantly, these patients were transferred with tracheostoma (76%) to rehabilitation units (44%) by specialized physician-assisted patient transport ambulances (75%). DISCUSSION: The transfer of ventilated patients after initial ICU stay is a relevant issue for interhospital transfer. Routine documentation of a structured weaning process is sufficient in core elements to describe the weaning process. This is of great importance for continuity in the further treatment of these patients.

Virus variant-specific clinical performance of SARS coronavirus two rapid antigen tests in point-of-care use, from November 2020 to January 2022.

OBJECTIVES: Antigen rapid diagnostic tests (RDTs) for SARS coronavirus 2 (SARS-CoV-2) are quick, widely available, and inexpensive. Consequently, RDTs have been established as an alternative and additional diagnostic strategy to quantitative reverse transcription polymerase chain reaction (RT-qPCR). However, reliable clinical and large-scale performance data specific to a SARS-CoV-2 virus variant of concern (VOC) are limited, especially for the Omicron VOC. The aim of this study was to compare RDT performance among different VOCs. METHODS: This single-centre prospective performance assessment compared RDTs from three manufacturers (NADAL, Panbio, MEDsan) with RT-qPCR including deduced standardized viral load from oropharyngeal swabs for detection of SARS-CoV-2 in a clinical point-of-care setting from November 2020 to January 2022. RESULTS: Among 35 479 RDT/RT-qPCR tandems taken from 26 940 individuals, 164 of the 426 SARS-CoV-2 positive samples tested true positive with an RDT corresponding to an RDT sensitivity of 38.50% (95% CI, 34.00-43.20%), with an overall specificity of 99.67% (95% CI, 99.60-99.72%). RDT sensitivity depended on viral load, with decreasing sensitivity accompanied by descending viral load. VOC-dependent sensitivity assessment showed a sensitivity of 42.86% (95% CI, 32.82-53.52%) for the wild-type SARS-CoV-2, 43.42% (95% CI, 32.86-54.61%) for the Alpha VOC, 37.67% (95% CI, 30.22-45.75%) for the Delta VOC, and 33.67% (95% CI, 25.09-43.49%) for the Omicron VOC. Sensitivity in samples with high viral loads of ≥106 SARS-CoV-2 RNA copies per mL was significantly lower in the Omicron VOC (50.00%; 95% CI, 36.12-63.88%) than in the wild-type SARS-CoV-2 (79.31%; 95% CI, 61.61-90.15%; p 0.015). DISCUSSION: RDT sensitivity for detection of the Omicron VOC is reduced in individuals infected with a high viral load, which curtails the effectiveness of RDTs. This aspect furthert: limits the use of RDTs, although RDTs are still an irreplaceable diagnostic tool for rapid, economic point-of-care and extensive SARS-CoV-2 screening.

Uncoupling of platelet granule release and integrin activation suggests GPIIb/IIIa as a therapeutic target in COVID-19.

Thromboembolic events are frequent and life-threating complications of COVID-19 but are also observed in patients with sepsis. Disseminated thrombosis can occur despite anticoagulation, suggesting that platelets play a direct but incompletely understood role. Several studies demonstrated altered platelet function in COVID-19 with some controversial findings, while underlying disease-specific mechanisms remain ill defined. We performed a comprehensive cohort study with 111 patients, comprising 37 with COVID-19, 46 with sepsis, and 28 with infection, compared with control participants. Platelet phenotype and function were assessed under static and flow conditions, revealing unexpected disease-specific differences. From hospital admission onward, platelets in COVID-19 failed to activate the integrin glycoprotein IIb/IIa (GPIIb/IIIa) in response to multiple agonists. Dense granule release was markedly impaired due to virtually missing granules, also demonstrated by whole-mount electron microscopy. By contrast, α-granule marker CD62P exposure was only mildly affected, revealing a subpopulation of PAC-1-/CD62P+ platelets, independently confirmed by automated clustering. This uncoupling of α-granule release was not observed in patients with sepsis, despite a similar disease severity. We found overall unaltered thrombus formation in COVID-19 and sepsis samples under venous shear rates, which was dependent on the presence of tissue factor. Unexpectedly, under arterial shear rates, thrombus formation was virtually abrogated in sepsis, whereas we detected overall normal-sized and stable thrombi in blood from patients with COVID-19. These thrombi were susceptible to subthreshold levels of GPIIb/IIIa blockers, eptifibatide, or tirofiban that had only a minor effect in control participants' blood. We provide evidence that low-dose GPIIb/IIIa blockade could be a therapeutic approach in COVID-19.

Medical and cardio-vascular emergency department visits during the COVID-19 pandemic in 2020: is there a collateral damage? A retrospective routine data analysis.

BACKGROUND: In this retrospective routine data analysis, we investigate the number of emergency department (ED) consultations during the COVID-19 pandemic of 2020 in Germany compared to the previous year with a special focus on numbers of myocardial infarction and acute heart failure. METHODS: Aggregated case numbers for the two consecutive years 2019 and 2020 were obtained from 24 university hospitals and 9 non-university hospitals in Germany and assessed by age, gender, triage scores, disposition, care level and by ICD-10 codes including the tracer diagnoses myocardial infarction (I21) and heart failure (I50). RESULTS: A total of 2,216,627 ED consultations were analyzed, of which 1,178,470 occurred in 2019 and 1,038,157 in 2020. The median deviation in case numbers between 2019 and 2020 was - 14% [CI (- 11)-(- 16)]. After a marked drop in all cases in the first COVID-19 wave in spring 2020, case numbers normalized during the summer. Thereafter starting in calendar week 39 case numbers constantly declined until the end of the year 2020. The decline in case numbers predominantly concerned younger [- 16%; CI (- 13)-(- 19)], less urgent [- 18%; CI (- 12)-(- 22)] and non-admitted cases [- 17%; CI (- 13)-(- 20)] in particular during the second wave. During the entire observation period admissions for chest pain [- 13%; CI (- 21)-2], myocardial infarction [- 2%; CI (- 9)-11] and heart failure [- 2%; CI (- 10)-6] were less affected and remained comparable to the previous year. CONCLUSIONS: ED visits were noticeably reduced during both SARS-CoV-2 pandemic waves in Germany but cardiovascular diagnoses were less affected and no refractory increase was noted. However, long-term effects cannot be ruled out and need to be analysed in future studies.

Effect of therapeutic drug monitoring-based dose optimization of piperacillin/tazobactam on sepsis-related organ dysfunction in patients with sepsis: a randomized controlled trial.

PURPOSE: Insufficient antimicrobial exposure is associated with worse outcomes in sepsis. We evaluated whether therapeutic drug monitoring (TDM)-guided antibiotic therapy improves outcomes. METHODS: Randomized, multicenter, controlled trial from January 2017 to December 2019. Adult patients (n = 254) with sepsis or septic shock were randomly assigned 1:1 to receive continuous infusion of piperacillin/tazobactam with dosing guided by daily TDM of piperacillin or continuous infusion with a fixed dose (13.5 g/24 h if eGFR ≥ 20 mL/min). Target plasma concentration was four times the minimal inhibitory concentration (range ± 20%) of the underlying pathogen, respectively, of Pseudomonas aeruginosa in empiric situation. Primary outcome was the mean of daily total Sequential Organ Failure Assessment (SOFA) score up to day 10. RESULTS: Among 249 evaluable patients (66.3 ± 13.7 years; female, 30.9%), there was no significant difference in mean SOFA score between patients with TDM (7.9 points; 95% CI 7.1-8.7) and without TDM (8.2 points; 95% CI 7.5-9.0) (p = 0.39). Patients with TDM-guided therapy showed a lower 28-day mortality (21.6% vs. 25.8%, RR 0.8, 95% CI 0.5-1.3, p = 0.44) and a higher rate of clinical (OR 1.9; 95% CI 0.5-6.2, p = 0.30) and microbiological cure (OR 2.4; 95% CI 0.7-7.4, p = 0.12), but these differences did not reach statistical significance. Attainment of target concentration was more common in patients with TDM (37.3% vs. 14.6%, OR 4.5, CI 95%, 2.9-6.9, p < 0.001). CONCLUSION: TDM-guided therapy showed no beneficial effect in patients with sepsis and continuous infusion of piperacillin/tazobactam with regard to the mean SOFA score. Larger studies with strategies to ensure optimization of antimicrobial exposure are needed to definitively answer the question.

Plasma Metabolome Profiling for the Diagnosis of Catecholamine Producing Tumors.

Context: Pheochromocytomas and paragangliomas (PPGL) cause catecholamine excess leading to a characteristic clinical phenotype. Intra-individual changes at metabolome level have been described after surgical PPGL removal. The value of metabolomics for the diagnosis of PPGL has not been studied yet. Objective: Evaluation of quantitative metabolomics as a diagnostic tool for PPGL. Design: Targeted metabolomics by liquid chromatography-tandem mass spectrometry of plasma specimens and statistical modeling using ML-based feature selection approaches in a clinically well characterized cohort study. Patients: Prospectively enrolled patients (n=36, 17 female) from the Prospective Monoamine-producing Tumor Study (PMT) with hormonally active PPGL and 36 matched controls in whom PPGL was rigorously excluded. Results: Among 188 measured metabolites, only without considering false discovery rate, 4 exhibited statistically significant differences between patients with PPGL and controls (histidine p=0.004, threonine p=0.008, lyso PC a C28:0 p=0.044, sum of hexoses p=0.018). Weak, but significant correlations for histidine, threonine and lyso PC a C28:0 with total urine catecholamine levels were identified. Only the sum of hexoses (reflecting glucose) showed significant correlations with plasma metanephrines.By using ML-based feature selection approaches, we identified diagnostic signatures which all exhibited low accuracy and sensitivity. The best predictive value (sensitivity 87.5%, accuracy 67.3%) was obtained by using Gradient Boosting Machine Modelling. Conclusions: The diabetogenic effect of catecholamine excess dominates the plasma metabolome in PPGL patients. While curative surgery for PPGL led to normalization of catecholamine-induced alterations of metabolomics in individual patients, plasma metabolomics are not useful for diagnostic purposes, most likely due to inter-individual variability.

Clinical performance evaluation of SARS-CoV-2 rapid antigen testing in point of care usage in comparison to RT-qPCR.

BACKGROUND: Antigen rapid diagnostic tests (RDT) for SARS-CoV-2 are fast, broadly available, and inexpensive. Despite this, reliable clinical performance data from large field studies is sparse. METHODS: In a prospective performance evaluation study, RDT from three manufacturers (NADAL®, Panbio™, MEDsan®, conducted on different samples) were compared to quantitative reverse transcription polymerase chain reaction (RT-qPCR) in 5 068 oropharyngeal swabs for detection of SARS-CoV-2 in a hospital setting. Viral load was derived from standardised RT-qPCR Cycle threshold (Ct) values. The data collection period ranged from November 12, 2020 to February 28, 2021. FINDINGS: The sensitivity of RDT compared to RT-qPCR was 42·57% (95% CI 33·38%-52·31%). The specificity was 99·68% (95% CI 99·48%-99·80%). Sensitivity declined with decreasing viral load from 100% in samples with a deduced viral load of ≥108 SARS-CoV-2 RNA copies per ml to 8·82% in samples with a viral load lower than 104 SARS-CoV-2 RNA copies per ml. No significant differences in sensitivity or specificity could be observed between samples with and without spike protein variant B.1.1.7. The NPV in the study cohort was 98·84%; the PPV in persons with typical COVID-19 symptoms was 97·37%, and 28·57% in persons without or with atypical symptoms. INTERPRETATION: RDT are a reliable method to diagnose SARS-CoV-2 infection in persons with high viral load. RDT are a valuable addition to RT-qPCR testing, as they reliably detect infectious persons with high viral loads before RT-qPCR results are available. FUNDING: German Federal Ministry for Education and Science (BMBF), Free State of Bavaria.

COVID-19 and the kidney: A retrospective analysis of 37 critically ill patients using machine learning.

INTRODUCTION: There is evidence that SARS-CoV2 has a particular affinity for kidney tissue and is often associated with kidney failure. METHODS: We assessed whether proteinuria can be predictive of kidney failure, the development of chronic kidney disease, and mortality in 37 critically ill COVID-19 patients. We used machine learning (ML) methods as decision trees and cut-off points created by the OneR package to add new aspects, even in smaller cohorts. RESULTS: Among a total of 37 patients, 24 suffered higher-grade renal failure, 20 of whom required kidney replacement therapy. More than 40% of patients remained on hemodialysis after intensive care unit discharge or died (27%). Due to frequent anuria proteinuria measured in two-thirds of the patients, it was not predictive for the investigated endpoints; albuminuria was higher in patients with AKI 3, but the difference was not significant. ML found cut-off points of >31.4 kg/m2 for BMI and >69 years for age, constructed decision trees with great accuracy, and identified highly predictive variables for outcome and remaining chronic kidney disease. CONCLUSIONS: Different ML methods and their clinical application, especially decision trees, can provide valuable support for clinical decisions. Presence of proteinuria was not predictive of CKD or AKI and should be confirmed in a larger cohort.

Acquired platelet GPVI receptor dysfunction in critically ill patients with sepsis.

Glycoprotein VI (GPVI), the platelet immunoreceptor tyrosine activating motif (ITAM) receptor for collagen, plays a striking role on vascular integrity in animal models of inflammation and sepsis. Understanding ITAM-receptor signaling defects in humans suffering from sepsis may improve our understanding of the pathophysiology, especially during disease onset. In a pilot study, platelets from 15 patients with sepsis were assessed consecutively at day of admission, day 5 to 7, and the day of intensive care unit (ICU) discharge and subjected to comprehensive analyses by flow cytometry, aggregometry, and immunoblotting. Platelet function was markedly reduced in all patients. The defect was most prominent after GPVI stimulation with collagen-related peptide. In 14 of 15 patients, GPVI dysfunction was already present at time of ICU admission, considerably before the critical drop in platelet counts. Sepsis platelets failed to transduce the GPVI-mediated signal to trigger tyrosine phosphorylation of Syk kinase or LAT. GPVI deficiency was partially inducible in platelets of healthy donors through coincubation in whole blood, but not in plasma from patients with sepsis. Platelet aggregation upon GPVI stimulation increased only in those patients whose condition ameliorated. As blunted GPVI signaling occurred early at sepsis onset, this defect could be exploited as an indicator for early sepsis diagnosis, which needs to be confirmed in prospective studies.

Treatment of symptomatic hyponatremia with hypertonic saline: a real-life observational study.

OBJECTIVE: Treatment of symptomatic hyponatremia is not well established. The European guidelines recommend bolus-wise administration of 150 mL of 3% hypertonic saline. This recommendation is, however, based on low level of evidence. DESIGN: Observational study. METHODS: Sixty-two consecutive hyponatremic patients admitted to the emergency department or intensive care unit of the University Hospital Wuerzburg were divided in subgroups according to treatment (150 mL bolus of 3% hypertonic saline or conventional treatment) and symptom severity. Treatment target was defined as an increase in serum sodium by 5-10 mEq/L within first 24 h and maximum 8 mEq/L during subsequent 24 h. RESULTS: Thirty-three out of sixty-two patients (53%) were presented with moderate symptoms and 29/62 (47%) with severe symptoms. Thirty-six were treated with hypertonic saline and 26 conventionally. In the hypertonic saline group, serum sodium increased from 116 ± 7 to 123 ± 6 (24 h) and 127 ± 6 mEq/L (48 h) and from 121 ± 6 to 126 ± 5 and 129 ± 4 mEq/L in the conventional group, respectively. Overcorrection at 24 h occurred more frequent in patients with severe symptoms than with moderate symptoms (38% vs 6%, P < 0.05). Diuresis correlated positively with the degree of sodium overcorrection at 24 h (r = 0.6, P < 0.01). Conventional therapies exposed patients to higher degrees of sodium fluctuations and an increased risk for insufficient sodium correction at 24 h compared to hypertonic saline (RR: 2.8, 95% CI: 1.4-5.5). CONCLUSION: Sodium increase was more constant with hypertonic saline, but overcorrection rate was high, especially in severely symptomatic patients. Reducing bolus-volume and reevaluation before repeating bolus infusion might prevent overcorrection. Symptoms caused by hypovolemia can be misinterpreted as severely symptomatic hyponatremia and diuresis should be monitored.

[Pericardiocentesis - step by step]. / Perikardpunktion ­ Schritt für Schritt.

A pericardial effusion can be caused by malignant, infectious and autoimmune diseases or by trauma, such as a coronary artery rupture during a cath procedure. In the case of a cardiac tamponade a pericardiocentesis has to be performed immediately.Additionally, a pericardiocentesis may also be performed for diagnostic purposes. However, since histologic and microbiologic findings are rarely pointing to hitherto unsuspected results, the risk of the procedure must very carefully be weighed against its benefits. The risks of a pericardiocentesis include injuries to the lungs and liver as well as the heart itself, such as puncture of the right ventricle or the rupture of a coronary artery.This article is a step-by-step description of how to safely perform an ultrasound-guided pericardiocentesis.

Pro- and Anti-Inflammatory Responses in Severe COVID-19-Induced Acute Respiratory Distress Syndrome-An Observational Pilot Study.

Objectives: The severity of Coronavirus Disease 2019 (COVID-19) is largely determined by the immune response. First studies indicate altered lymphocyte counts and function. However, interactions of pro- and anti-inflammatory mechanisms remain elusive. In the current study we characterized the immune responses in patients suffering from severe COVID-19-induced acute respiratory distress syndrome (ARDS). Methods: This was a single-center retrospective study in patients admitted to the intensive care unit (ICU) with confirmed COVID-19 between March 14th and May 28th 2020 (n = 39). Longitudinal data were collected within routine clinical care, including flow-cytometry of lymphocyte subsets, cytokine analysis and growth differentiation factor 15 (GDF-15). Antibody responses against the receptor binding domain (RBD) of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Spike protein were analyzed. Results: All patients suffered from severe ARDS, 30.8% died. Interleukin (IL)-6 was massively elevated at every time-point. The anti-inflammatory cytokine IL-10 was concomitantly upregulated with IL-6. The cellular response was characterized by lymphocytopenia with low counts of CD8+ T cells, natural killer (NK) and naïve T helper cells. CD8+ T and NK cells recovered after 8 to 14 days. The B cell system was largely unimpeded. This coincided with a slight increase in anti-SARS-CoV-2-Spike-RBD immunoglobulin (Ig) G and a decrease in anti-SARS-CoV-2-Spike-RBD IgM. GDF-15 levels were elevated throughout ICU treatment. Conclusions: Massively elevated levels of IL-6 and a delayed cytotoxic immune defense characterized severe COVID-19-induced ARDS. The B cell response and antibody production were largely unimpeded. No obvious imbalance of pro- and anti-inflammatory mechanisms was observed, with elevated GDF-15 levels suggesting increased tissue resilience.