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Introduction: Longitudinal studies of lung function following COVID-19 remain limited. This study examined lung function in COVID-19 patients for two years after discharge from an intensive care unit (ICU).

Methods: Patients treated for COVID-19 in Uppsala ICU (mean 11.1 days) were assessed at four months, one year, and two years post-discharge. Lung function tests included spirometry, diffusing capacity for carbon monoxide (D_Lco), and body plethysmography. Logistic regression adjusted for age, sex, and body mass index (BMI) assessed the association between impaired D_Lco and patients' characteristics.

Result: A total of 104 patients (32% female, with a mean age of 60 years) participated in four months follow-up, 40 in one year follow-up, and 21 in two years follow-up after discharge. Impaired D_Lco was observed in 50%, 58%, and 33% of patients at four months, one year, and two years, respectively. A comparison showed that D_Lco% predicted declined from four months to one year (mean 79.0, SD 14.7, to 74.3, SD 15.7; p< 0.001), then improved between one and two years (p< 0.001). Forced vital capacity (FVC) % predicted improved between four months and one year (p < 0.001) and between one and two years (p = 0.004). Forced expiratory volume during the first second (FEV₁) % predicted improved only between four months and one year (p = 0.002). Total lung capacity improved between the one- and two-year follow-ups (p = 0.006). Impaired D(L)co at four months was significantly associated with age ≥ 60 years (adjusted odds ratios, 95% confidence interval: 6.73 (2.64-17.12), mechanical ventilation (4.74 (1.82-12.34), longer ICU stay (5.84 (2.13-16.01), minimum lymphocyte count at ICU (0.19 (0.04-0.83), and FVC % predicted (0.93 (0.89-0.96)) and FEV₁ % predicted (0.93 (0.89-0.97)).

Conclusion: Despite recovery between one and two years, one-third of patients exhibited impaired D(L)co two years after critical COVID-19, highlighting the need for pulmonary follow-up to address persistent lung function deficits.

Background: Several genes and genomic regions have been implicated in COVID-19 susceptibility and severity, but their clinical relevance remains uncertain. We comprehensively assessed both copy number variants (CNVs) and single-nucleotide variants (SNVs) disrupting genes implicated in COVID-19 in a Swedish cohort of ICU-treated COVID-19 patients with detailed phenotype data. Methods: Patients (n = 301) with severe COVID-19 treated in intensive care units (ICU) between March 2020 and January 2021 at two large Swedish university hospitals were included. Whole exome sequencing (WES) was performed to identify both large copy number variations (CNVs) and single-nucleotide variants (SNVs), including small indels, using the Genome Analysis Toolkit (GATK) pipelines. We focused our analyses on variants disrupting coding genes implicated in severe COVID-19, but also assessed variants known to cause human disease. Results: We identified 11 rare CNVs and several SNVs potentially linked to severe COVID-19. Patients carrying a CNV spanning a COVID-19-implicated gene had higher levels of the heart failure marker NT-proBNP (median 4440 [1558-8160] vs. 1170 [329-3152], p = 0.017), worse renal function at ICU admission (p = 0.0026), and a higher need for continuous renal replacement therapy (CRRT) (28% vs. 10%, p = 0.045) compared to patients without a potentially damaging CNV. Conclusions: Although patients with a potentially damaging CNV or SNV exhibited some differences in cardiac and renal markers, our findings do not support broad genetic screening as a predictive tool for COVID-19 severity.

Hyperosmolality is increasingly recognized as a factor contributing to severe COVID-19. Recently, a genetic variant near the aquaporin 3 (AQP3) water channel was associated with severe COVID-19 [rs60840586:G; odds ratio (OR): 1.07, P = 2.5 x 10(-9)]. The variant is known to increase gene expression of AQP3 in several organs, including the lung [normalized expression scores (NES) = 0.33, P = 4.1 x 10(-20)] in GTEx. In this study, we investigated 576 patients in the Biobanque Quebecoise de la COVID-19 (BQC-19) with both genetic and clinical data available. We estimated plasma osmolality using the formula: eOSM = 2 x [Na+] + 2 x [K+] + [Urea] + [Glucose]. Using a logistic regression of mortality against eOSM, genotype at rs60840586, sex, age, and the first 10 genetic principal components, we confirm that hyperosmolality is associated with COVID-19 mortality (OR = 2.06 [95% CI = 1.62-2.65], P = 9.13 x 10(-9)). Interestingly, we found that the risk of death linked to hyperosmolality is influenced by the AQP3 variant rs60840586:G genotype (OR = 1.95 [95% CI = 1.22-3.28], P = 0.0075). However, the rs60840586 genotype did not independently affect mortality in this cohort. These findings suggest that the body's ability to regulate and accommodate hyperosmolality may be disrupted by overexpression of AQP3, potentially worsening outcomes in COVID-19. Given the role of AQP3 in water transport and homeostasis, further defining the functionality of its variants may provide key insights into COVID-19 severity and guide clinical management strategies, particularly in critically ill patients with hyperosmolality.

BACKGROUND: Negative postoperative behaviour changes (NPOBC) are known to occur after general anaesthesia in children. A significantly increased risk of NPOBC has been reported in children who exhibited a reduction in cerebral regional oxygen saturation (crSO₂) of as little as 5% below baseline levels. These results were unexpected, and we therefore aimed to investigate the association between degrees of regional cerebral desaturation and NPOBC after routine surgery in young children.

METHODS: In this prospective cohort study, 180 healthy children between 2 and 6 years old undergoing routine surgery were enrolled. The primary outcome was NPOBC, assessed using the Post Hospitalization Behavior Questionnaire (PHBQ), reported by parents and evaluated on Postoperative Day 7. The results were stratified according to decreases in crSO₂ from baseline of at least 5, 10, 15 or 20 percentage points sustained for a minimum duration of 2 min. The χ² or Fisher's exact test was used to analyse differences in categorical variables. Using logistic regression, outcome data were expressed as odds ratios with 95% confidence intervals.

RESULTS: The incidence of NPOBC was 13% on Day 7, and 15% on Day 30, respectively. No significant differences were found between children with or without NPOBC for any of the thresholds of crSO₂ reduction (≥ 5%: 2 [11%] vs. 2 [1.8%] cases, p = 0.09; ≥ 10%: 1 [5.6%] vs. 2 [1.8%] cases, p = 0.36; ≥ 15% and ≥ 20%: 0 vs. 0 cases). The rate of NPOBC was not associated with intraoperative reduction in crSO₂ (OR 1.25, CI 0.71-2.20, p = 0.46). Older age was associated with lower odds of NPOBCs (OR 0.39, CI 0.15-0.99, p = 0.048). Using the area under the curve for quantifying crSO₂ changes did not result in a statistically significant correlation between crSO₂ and NPBOCs (r = 0.11).

CONCLUSION: Regional cerebral desaturation and negative postoperative behaviour may be less common than previously reported in young children undergoing uneventful general anaesthesia. We could not corroborate the strong association between these entities reported previously. Studies investigating the effects of cerebral desaturation on patient-centred outcomes will need large sample sizes.

EDITORIAL COMMENT: This prospective observational study describes a low incidence and magnitude of NIRS desaturation in healthy children. In contrast to previous reporting, there was no association with new negative postoperative behaviours in children in this cohort.

TRIAL REGISTRATION: ISCRTN11799594.

The aim of this study is to investigate the association between alcohol consumption and the risk of bacterial infection and its dose-response association. Participants in the Swedish Mammography Cohort and Cohort of Swedish Men answered lifestyle questionnaires in 1997 and have since been followed in national registers. The risks of acquiring infection, intensive care unit (ICU) admission and dying due to infection were assessed with Cox regression. Among 58,078 cohort participants followed for 23 years, 23,035 participants were diagnosed with an infection and 4,030 died from infection. Alcohol consumption exhibited a J-shaped association with the risk of acquiring infection and dying due to infection: compared to consuming 5-10 g of alcohol per day, consuming < 0.5 g/day and consuming > 30 g/day were both associated with higher risk of acquiring infection, ICU admission and dying due to infection, whereas alcohol consumption between 5 and 30 g/day was not associated with acquiring infection, ICU admission or death due to infection. In conclusion, moderate alcohol consumption was not associated with infection, but both very low and high levels of consumption were associated with acquiring infection, ICU admission and death. If replicated, this suggests that reduction of alcohol consumption might reduce mortality from bacterial infections.

Hemorrhage and hypotension leading to renal hypoperfusion are common causes of acute kidney injury (AKI). Anesthetic agents may affect renal hemodynamics, potentially altering renal outcomes during hypovolemia. This study evaluated the effects of two commonly used anesthetics, propofol and sevoflurane, on renal blood flow (RBF) and oxygenation during hemorrhage. Fourteen pigs (30 +/- 2 kg) were anesthetized with either propofol or sevoflurane, with fentanyl as an opioid supplement in both groups. Following baseline measurements, hemorrhage was induced to maintain a mean arterial pressure (MAP) below 50 mmHg for 30 min, after which resuscitation was performed using a 1:1 replacement of whole blood and Ringer's acetate. Acute renal function recovery was evaluated 1 h post resuscitation. At baseline, sevoflurane-anesthetized animals had lower RBF and renal oxygen delivery, and higher renal vascular resistance compared with the propofol group. During hemorrhage, the change in these variables was comparable. After resuscitation, cardiovascular and RBF recovery were similar between the groups. However, oxygen delivery remained significantly lower in the sevoflurane group compared with the propofol group. In addition, renal vascular resistance was significantly higher during sevoflurane anesthesia compared with propofol after recovery. In conclusion, compared with propofol anesthesia, sevoflurane anesthesia reduced RBF and renal oxygen delivery already at baseline. The difference in oxygen delivery persisted after hemorrhage, even though RBF was comparable between groups.

Background Preoperative fasting regimens designed to minimise the risk of pulmonary aspiration have undergone significant changes, but unequivocal evidence of the safety of reducing clear fluid fasting has been lacking. We compared the risk of pulmonary aspiration in children using three different recommendations for clear fluid fasting. Methods In this prospective multicentre cohort study, centres with >1000 paediatric anaesthesia cases per year were eligible. Regurgitation events, whether they were transient or led to consequences affecting postoperative care, were reported in detail. All centres also reported the number of anaesthetised children per year and which preoperative fasting regimen they used. Results The 31 participating centres contributed a total of 306 900 anaesthetic procedures. The incidence of confirmed pulmonary aspiration was 1.18:10 000 in the sip-til-send group, 0.96:10 000 in the >= 1 h group, and 1.83:10 000 in the control group. There was no mortality as a result of aspiration. The 95% confidence intervals of the differences in confirmed pulmonary aspiration between the control group and the >= 1 h clear fluid fasting and the sip-til-send group were -0.344 to 3.76 and -1.48 to 3.63, respectively. Both sip-til-send and >= 1 h clear fluid fasting were statistically noninferior to >= 2 h clear fluid fasting regarding the incidence of confirmed aspiration, transient regurgitation, and regurgitation leading to escalation of care or intensive care. Conclusions The study provides evidence for the safety of reducing preoperative fasting time for clear fluids in children aged <16 yr from 2 h to <= 1 h. <ol> </ol>

Severe coronavirus disease 2019 (COVID-19) is characterized by systemic hyperinflammation with cytokine and chemokine release, alongside elevations in conventional laboratory biomarkers such as C-reactive protein (CRP), ferritin, and procalcitonin (PCT). However, the interplay between cytokines, chemokines, growth factors (CCGFs), and standard biomarkers remains incompletely understood. Therefore, we aimed to evaluate associations between CCGFs and conventional biomarkers from a broad aspect, utilizing the prospective PronMed cohort of critically ill COVID-19 patients admitted to the intensive care unit (ICU) at Uppsala University Hospital. Plasma concentrations of 92 CCGFs were analyzed in each patient using the Olink Target 96 Cardiovascular II panel and analyzed in relation to conventional biomarkers and peripheral blood cell counts. Associations were evaluated using Spearman rank correlations with Benjamini–Hochberg correction for multiple testing. A total of 114 patients (median age 61 years (IQR: 19), 75% male, median SAPS-3 52 (IQR: 10) were included. Significant correlations confirmed CRP as a robust surrogate of cytokine-driven inflammation. Ferritin was strongly associated with macrophage-related markers, including IL-18, sCD163-related factors, and PARP1. PCT correlated with a wide range of CCGFs, including ADM, PGF, TRAILR2, and IL-6. Blood cell subsets also showed distinct associations with CCGFs, suggesting functional connections between cytokine signaling and hematological disturbances. Our findings demonstrate that conventional biomarkers of inflammation in COVID-19 reflect complex and distinct interaction patterns with cytokines, chemokines, and growth factors. Mapping these associations improves understanding of COVID-19 immunopathology and may inform biomarker-guided risk stratification in critical illness.

  Introduction

A decrease in renal perfusion during acute kidney injury (AKI) due to critical COVID-19 has previously been demonstrated. The objective of this study was to compare the effects of plasma expansion with a standardized fluid bolus on renal perfusion in critically ill patients with AKI compared to similar patients without AKI.

Methods

A case control study design was used to investigate group differences before and after a standardized intervention. ICU-treated COVID-19 patients without underlying kidney disease were assigned to two groups based on KDIGO Creatinine criteria for AKI. Renal perfusion was assessed by magnetic resonance imaging using phase contrast and arterial spin labeling before and directly after plasma expansion with 7.5 mL/kg Ringer's Acetate (Baxter). Arithmetic means of mean arterial pressures (MAP) recorded before and after plasma infusion were compared. Data was analyzed with a mixed model repeated measures ANOVA for all kidneys using a random effect to account for research subjects.

Results

Nine patients with AKI and eight without were included in the study. The hemodynamic response to plasma expansion was similar in both groups, with increases in MAP by 9 mmHg (95% CI 0.5–18) and 15 mmHg (95% CI 5–24) in patients with and without AKI, respectively. Total renal perfusion and cortical perfusion were not significantly changed by plasma expansion in either group. There was a reduction of medullary perfusion in patients without AKI from 55 (95% CI 39–79) to 34 (95% CI 24–48) mL/min/100 g (p = .0027).

Conclusion

Plasma expansion with a standardized fluid bolus did not increase renal perfusion in critically ill patients with COVID-19, with or without AKI.