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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.

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.

BACKGROUND: Hypernatremia, a common electrolyte disorder in critically ill patients, induces a hyperosmotic state linked to increased mortality and metabolic stress. While loop diuretics such as furosemide are used for fluid management, their main effect is water excretion, often worsening hypernatremia. This study aimed to determine whether free water infusion enhances sodium excretion when combined with furosemide after a sodium chloride bolus. We also hypothesized that hyperosmolar hypernatremia stimulates protein degradation and urea synthesis.

RESULTS: Fourteen pigs (seven per group) received a sodium chloride bolus to induce hypernatremia (plasma Na⁺ > 150 mmol/L). One group received furosemide alone, while the other received furosemide plus free water to maintain normo-osmolality. Renal and metabolic parameters were analyzed over five hours. Free water infusion significantly lowered plasma sodium levels (134 ± 4 vs. 150 ± 4 mmol/L, p = 1.2e-14) and increased total sodium excretion (99 ± 20 vs. 70 ± 18 mmol, p = 0.00056) and urine output (1860 ± 220 vs. 1200 ± 160 mL, p = 2.47e-05). Fractional sodium excretion was higher with free water (5.3 ± 1.1% vs. 3.5 ± 2.2%, p = 0.012). Plasma glutamine was elevated in the no-water group (1305 ± 209 vs. 1084 ± 110 µmol/L, p = 0.029), indicating greater metabolic stress.

CONCLUSIONS: These results suggest that free water infusion enhances sodium clearance and reduces hypernatremia-induced metabolic alterations, supporting its potential role in fluid management strategies.

Infections can lead to persistent symptoms and diseases such as shingles after varicella zoster or rheumatic fever after streptococcal infections. Similarly, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can result in long coronavirus disease (COVID), typically manifesting as fatigue, pulmonary symptoms and cognitive dysfunction. The biological mechanisms behind long COVID remain unclear. We performed a genome-wide association study for long COVID including up to 6,450 long COVID cases and 1,093,995 population controls from 24 studies across 16 countries. We discovered an association of FOXP4 with long COVID, independent of its previously identified association with severe COVID-19. The signal was replicated in 9,500 long COVID cases and 798,835 population controls. Given the transcription factor FOXP4's role in lung physiology and pathology, our findings highlight the importance of lung function in the pathophysiology of long COVID.

Background: Since its inception in 1974, the Essential Programme on Immunization (EPI) has achieved remarkable success, averting the deaths of an estimated 154 million children worldwide through routine childhood vaccination. However, more recent decades have seen persistent coverage inequities and stagnating progress, which have been further amplified by the COVID-19 pandemic. In 2019, WHO set ambitious goals for improving vaccine coverage globally through the Immunization Agenda 2030 (IA2030). Now halfway through the decade, understanding past and recent coverage trends can help inform and reorient strategies for approaching these aims in the next 5 years.

Methods: Based on the Global Burden of Diseases, Injuries, and Risk Factors Study 2023, this study provides updated global, regional, and national estimates of routine childhood vaccine coverage from 1980 to 2023 for 204 countries and territories for 11 vaccine-dose combinations recommended by WHO for all children globally. Employing advanced modelling techniques, this analysis accounts for data biases and heterogeneity and integrates new methodologies to model vaccine scale-up and COVID-19 pandemic-related disruptions. To contextualise historic coverage trends and gains still needed to achieve the IA2030 coverage targets, we supplement these results with several secondary analyses: (1) we assess the effect of the COVID-19 pandemic on vaccine coverage; (2) we forecast coverage of select life-course vaccines up to 2030; and (3) we analyse progress needed to reduce the number of zero-dose children by half between 2023 and 2030.

Findings: Overall, global coverage for the original EPI vaccines against diphtheria, tetanus, and pertussis (first dose [DTP1] and third dose [DTP3]), measles (MCV1), polio (Pol3), and tuberculosis (BCG) nearly doubled from 1980 to 2023. However, this long-term trend masks recent challenges. Coverage gains slowed between 2010 and 2019 in many countries and territories, including declines in 21 of 36 high-income countries and territories for at least one of these vaccine doses (excluding BCG, which has been removed from routine immunisation schedules in some countries and territories). The COVID-19 pandemic exacerbated these challenges, with global rates for these vaccines declining sharply since 2020, and still not returning to pre-COVID-19 pandemic levels as of 2023. Coverage for newer vaccines developed and introduced in more recent years, such as immunisations against pneumococcal disease (PCV3) and rotavirus (complete series; RotaC) and a second dose of the measles vaccine (MCV2), saw continued increases globally during the COVID-19 pandemic due to ongoing introductions and scale-ups, but at slower rates than expected in the absence of the pandemic. Forecasts to 2030 for DTP3, PCV3, and MCV2 suggest that only DTP3 would reach the IA2030 target of 90% global coverage, and only under an optimistic scenario. The number of zero-dose children, proxied as children younger than 1 year who do not receive DTP1, decreased by 74·9% (95% uncertainty interval 72·1-77·3) globally between 1980 and 2019, with most of those declines reached during the 1980s and the 2000s. After 2019, counts of zero-dose children rose to a COVID 19-era peak of 18·6 million (17·6-20·0) in 2021. Most zero-dose children remain concentrated in conflict-affected regions and those with various constraints on resources available to put towards vaccination services, particularly sub-Saharan Africa. As of 2023, more than 50% of the 15·7 million (14·6-17·0) global zero-dose children resided in just eight countries (Nigeria, India, Democratic Republic of the Congo, Ethiopia, Somalia, Sudan, Indonesia, and Brazil), emphasising persistent inequities.

Interpretation: Our estimates of current vaccine coverage and forecasts to 2030 suggest that achieving IA2030 targets, such as halving zero-dose children compared with 2019 levels and reaching 90% global coverage for life-course vaccines DTP3, PCV3, and MCV2, will require accelerated progress. Substantial increases in coverage are necessary in many countries and territories, with those in sub-Saharan Africa and south Asia facing the greatest challenges. Recent declines will need to be reversed to restore previous coverage levels in Latin America and the Caribbean, especially for DTP1, DTP3, and Pol3. These findings underscore the crucial need for targeted, equitable immunisation strategies. Strengthening primary health-care systems, addressing vaccine misinformation and hesitancy, and adapting to local contexts are essential to advancing coverage. COVID-19 pandemic recovery efforts, such as WHO's Big Catch-Up, as well as efforts to bolster routine services must prioritise reaching marginalised populations and target subnational geographies to regain lost ground and achieve global immunisation goals. 

Introduction Functional recovery after intensive care is an important patient-centered outcome. In this study, we investigated risk factors for poor outcome after intensive care for sepsis using serial health-related quality of life (HRQoL) assessments and the burden of work incapacity as an objective proxy for functional recovery.

Methods We acquired data on all adult intensive care unit (ICU) patients with sepsis in Sweden between 2008 and 2020. Primary outcome was HRQoL assessed with RAND-36 at follow-up after ICU discharge. Sick-leave information was acquired on the working-age subpopulation to assess the burden of work incapacity.

Results RAND-36 data were available for 14,006 individuals and was lower than Swedish population reference levels. Males had higher RAND-36. Age had varying associations. Pre-ICU comorbidities were associated with lower RAND-36, whereas severity of illness was associated with lower general health. Invasive ventilation was associated with higher RAND-36, while continuous renal replacement therapy and length of stay (LoS) were associated with lower RAND-36. RAND-36 increased with time after ICU. Sick-leave length was associated with lower RAND-36. High levels of sick leave were seen in patients before intensive care for sepsis, suggesting pre-existing vulnerability. Sick leave increased further after sepsis and did not return to baseline, suggesting incomplete functional recovery, with lower education, female sex, and comorbidities as risk factors.

Conclusions In conclusion, in a Swedish national cohort of ICU patients surviving sepsis, HRQoL was low but improved over time. Severity of illness had minimal impact on HRQoL, while LoS and comorbidities were negative factors. Functional recovery in the form of days on sick leave showed a similar pattern. Study registration: The study was registered with clinicaltrials.gov: NCT06368336, on the 15th of April 2024.