Logo: to the web site of Uppsala University

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: Sepsis-induced immunosuppression impairs bacterial clearance and increases mortality. Liver and spleen macrophages are an essential part of the mononuclear phagocyte system and crucial for bacterial elimination. Systemic inflammation hampers bacterial clearance in the liver. We hypothesized that immunosuppression due to systemic inflammation might lead to decreased bacterial clearance by the spleen.

METHODS: Anesthetized pigs were subjected to an E. coli infusion for three hours in an intensive care setting. The Naive group only received the bacterial infusion (n = 10). The ETX group (n = 10) received an endotoxin infusion for 24 h, inducing systemic inflammation before the E. coli infusion. The Control group (n = 3) received saline instead of endotoxin for 24 h to study the effects of anesthesia alone. Bacterial counts and endotoxin levels were analyzed during the E. coli infusion. The levels of IL-6 and TNF were analyzed, and the piglets' physiological response was evaluated.

RESULTS: There was no difference in the bacterial counts in the artery, splenic vein or hepatic vein. However, the splenic venous to arterial bacterial counts ratio at 1-3 h was lower in Naive compared to ETX group (0.54 (0.34-1.07), 0.54 (0.20-0.85), 0.52 (0.21-0.64) vs. 0.77 (0.61-1.06), 0.85 (0.63-0.89), 0.74 (0.53-0.88); p < 0.01), but there was no difference in the animals' blood ex vivo bactericidal capacity. There was no difference in endotoxin clearance in the spleen between the groups. The peak log IL-6 and TNF levels in response to the E. coli infusion were higher in the Naive compared to the ETX group (3.40 ± 0.41 vs. 2.94 ± 0.43 pg × mL^-1 and 3.78 ± 0.68 vs. 2.23 ± 0.36 pg × mL^-1; p < 0.05 and p < 0.001, respectively). The respiratory, circulatory and metabolic response to the E. coli infusion was dampened in the animals pre-exposed to endotoxin.

CONCLUSION: The splenic bacterial clearance is impaired by pre-existing systemic inflammation, while differences in endotoxin elimination were not detected. The inflammatory and physiological response to bacteremia is diminished during ongoing inflammation. Since the animals' ex vivo bactericidal capacity was not affected by pre-existing inflammation, our results suggest that inherent mechanisms in the spleen were involved.

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.

The human blood proteome provides a holistic readout of health states through the assessment of thousands of circulating proteins. Here, we present a pan-disease resource to enable the study of diverse disease phenotypes within a harmonized proteomics dataset. By profiling protein concentrations across 59 diseases and healthy cohorts, we identified proteins associated with age, sex, and BMI, as well as disease-specific signatures. This study highlights shared and distinct protein patterns across conditions, demonstrating the power of a unified proteomics approach to uncover biological insights. The dataset, covering 8,262 individuals and up to 5,416 proteins, serves as an online resource for exploring disease-specific protein profiles and advancing precision medicine research.

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.

Calprotectin is a 24 kD heterodimer of calcium-binding proteins S100A8 and S100A9. At present, there is a lack of knowledge about the specificity of various methods for calprotectin detection, whether they measure only dimers between S100A8 and S100A9, S100A8-S100A8 dimers, S100A9/S100A9 dimers, or free subunits. This study aimed to compare total calprotectin levels with those of its subunits, S100A8 and S100A9, in ICU patients. This prospective observational study includes 271 sepsis and non-sepsis patients. Inclusion criteria were admission to intensive care and the presence or need for an arterial catheter. Plasma total calprotectin was measured at ICU admission and the following two days by particle-enhanced turbidimetric (PETIA) calprotectin reagents from Gentian AS and a Mindray BS380 chemistry analyzer. S100A8 and S100A9 were analyzed by commercial sandwich ELISA DY4570-05, and DY5578, R&D Systems, respectively. Sepsis was defined according to Sepsis-3 as suspected infection and a Sequential organ failure assessment (SOFA) >2 on admission. Receiver operating characteristic (ROC) analysis showed that total calprotectin had a larger area under the curve (AUC) for distinguishing sepsis from non-sepsis patients (0.67) compared to S100A8 (0.59) and S100A9 (0.52). For predicting 30-day mortality, S100A9 had a higher AUC value (0.64) than S100A8 (0.59). However, correlations between total calprotectin and its subunits were weak, indicating no significant relationship for predicting 30-day mortality, and highlighting potential issues with assay harmonization across manufacturers.

Background: Medical students navigate a complex landscape of digital tools with potential to enhance learning. The main objectives of the current study were to investigate which digital resources are being used, which background factors are associated with utilization, perceived advantages and disadvantages of different digital resources, and explore future directions.

Methods: Cross-sectional, nationwide, online 25-item multiple-choice question survey and one free-text question enabling qualitative data analysis. Medical students at all seven universities with medical school programs in Sweden were invited to participate. Data were collected October - December 2024.

Results: One thousand seven hundred sixty-six students responded to the survey, with an average response rate of 20.2% across sites. The five most frequently used digital resources were (percentage using at least on a weekly basis): University study platform (75.3%), videos (68.0%), flashcards (66.4%), student notes (53.4%) and external study platforms (47.3%). Flashcards were perceived to have a large to very large positive impact on development and maintenance of theoretical knowledge by 63.7% of students. Younger age (≤ 25 years) was strongly associated with higher use of flashcards (OR 1.98 (95% CI 1.54-2.54)) and generative artificial intelligence (AI) (OR 1.66 (1.29-2.15)), whereas having children at home was associated with more frequent use of videos (OR 2.32 (1.32-4.08)) and university digital platforms (OR 2.62 (1.26-5.45)), in multivariable logistic regression analyses. Most students (74.8%) reported finding their digital resources based on recommendations from more senior medical students. Perceived key advantages of digital resources in general were availability (90.9%), flexibility (80.6%), and more effective learning compared to traditional modalities (59.0%), while possible disadvantages included risk for distraction (49.6%) and uncertainty regarding reliability of content (45.4%). Qualitative data highlighted several areas of interest, including calls for universities and lecturers to provide high-quality, updated video material and flashcard decks tailored to the curriculum, and review and recommend third-party digital resources (e.g., YouTube channels).

Conclusions: Medical students extensively use digital resources, with perceived large positive learning effects and benefits. Several background factors influence usage patterns. These data may support institutions, program directors and teachers in their efforts to guide and improve use of digital learning tools in medical schools.