Acute Disease Severity Research Articles

Correlation between LDL/HDL-cholesterol ratio and long term prognosis after acute coronary syndrome and severity of coronary artery disease

Abstract Introduction Dyslipidaemia is an important correctable risk factor for coronary artery disease (CAD). Many studies have confirmed that the lower the low-density lipoprotein cholesterol (LDL-C) levels are, the lower is the CAD morbidity and mortality rates (1). However, many patients who achieved low levels of LDL-C still experience a major adverse cardiovascular event (MACE) because of the other residual risk factors. Therefore, there is a constant need for better stratification of patients who are at higher risk for novel MACE following their first acute coronary syndrome (ACS). Evidence increasingly suggests that the ratio of LDL-C/HDL-C might be a new and better marker of cardiovascular disease, as it simultaneously evaluates the levels of both LDL-C and HDL-C (2). Purpose The aim of this study was to investigate the prediction value of LDL-C/HDL-C ratio for long term prognosis after ACS as well as its correlation with CAD severity. Methods We included patients hospitalized at out centre with ACS from January 2017 to January 2024. Demographic data, data on LDL-C and HDL-C levels on admission and calculated Syntax score were used. Syntax score is a comprehensive angiographic scoring system which determines complexity by using coronary anatomy and lesion characteristics (3). Follow-up data were collected either by clinical follow-up visits or by telephone interviews. The MACE was defined as the composite of cardiovascular death, acute coronary syndrome and need for elective or urgent percutaneous or surgical revascularization. Results This registry-based study included 2471 patients with ACS, median age of 64 (interquartile range 56-73) years, 31% female. Total of 1099 patients (44%) had non-ST elevation ACS and 1372 (54%) had ST elevation myocardial infarction (STEMI). Median Syntax score was 13 (IQR 7-20.5), with 1494 (61%) patients having low Syntax score (≤16), 508 (21%) patients medium (16-22), and 448 (18%) high score (>22), respectively. Median follow up was 17 (3-27) months. LDL-C/HDL-C ratio correlated significantly with cardiovascular death, with weak coefficient (2.94 vs. 2.54 p<0.001; rho=0.102, p<.0001), however did not correlate with MACE (2.88 vs. 2.92, p=0.188, rho=0.06, p=0.77). This remained identical when tested for patients with STEMI and non-STE ACS. In addition, LDL-C/HDL-C ratio did not correlate with CAD severity as assessed with Syntax score (low 2.92 vs. medium 2.83 vs. high 2.86, p=0.597; rho=0.4, p=0.09). Conclusion Our data suggest that LDL-C/HDL-C ratio cannot be used as a relevant predictor of post-ACS long-term MACE or cardiovascular death, nor it can be correlated with CAD severity. Further studies are needed to establish the real value of LDL-C/HDL-C ratio as a post-ACS predictor.

A sex-based analysis of complete blood count features during acute, untreated Lyme disease

IntroductionAlthough lymphopenia has been described in acute Lyme disease (LD), the complete blood count (CBC) has not been comprehensively examined, nor have sex-based analyses been conducted. We analyzed CBC values and identified sex-based trends among patients with early LD by comparing both to controls without a history of LD and to patients’ pre-morbid values.MethodsWe enrolled participants from the Mid-Atlantic US with diagnostic erythema migrans and controls with no history of LD. CBC results were obtained, and patient information was recorded using standardized instruments. We also calculated a neutrophil-to-lymphocyte ratio (NLR). We used linear regression to test that CBC results would differ (a) between antibiotic-naive patients with early LD and controls and (b) by measures of acute disease severity. We also performed stratified analyses to assess sex-based differences.ResultsIn total, 236 antibiotic-naive patients with early LD had significantly lower lymphocytes (β = −0.34, p < 0.001) and significantly higher monocytes (β = 0.09, p = 0.002) and NLRs (β = 0.99, p < 0.001) than 61 controls in adjusted analyses. Lymphocytes, monocytes, and NLRs also changed significantly from pre-morbid to acute LD (p < 0.001 for all). Only the NLR was consistently significantly associated with disease severity. A higher proportion of male patients with early LD had acute lymphopenia than female patients with early LD (31.93% vs. 19.66%, p = 0.03); this difference was not present among controls.ConclusionThe presence of lymphopenia and the absence of an elevated total white blood cell count make LD an important diagnostic consideration in patients presenting with undiagnosed infectious syndromes in endemic regions. This may be especially true for male patients.

Lung Ultrasound Score, Severity of Acute Lung Disease and Prolonged Mechanical Ventilation in Children.

Lung ultrasound may be useful for prognostication of acute lung disease. To assess whether the lung ultrasound score is associated with the severity of lung disease and may predict prolonged invasive mechanical ventilation in critically ill children. Prospective observational multicenter study in children aged 1 month to 18 years who required respiratory support in the intensive care unit. Children with chronic parenchymal lung disease were excluded. The lung ultrasound score was obtained at 12 hours and 48-72 hours from admission. Prolonged invasive mechanical ventilation was defined as >7 consecutive days. Correlation of the lung ultrasound score with oxygenation as well as its prognostic accuracy for prolonged invasive mechanical ventilation were investigated. 538 children were included and 62 (11.5%) required prolonged mechanical ventilation. In these subjects, the lung ultrasound score was higher at 12 [24 (19-26) vs. 8 (3-14); p<0.001] and 48-72 hours [16 (10.5-22.5) vs. 6 (3-11) vs; p<0.001]. At 12 hours the lung ultrasound score correlated with oxygenation index [R2= 0.435 (95% CI: 0.293-0.566), rho coefficient -0.705, p<0.001] and oxygen saturation index [R2 0.499 (95% CI: 0.370-0.613), rho coefficient 0.651, p<0.001p<0.001]. To predict prolonged invasive mechanical ventilation, the lung ultrasound score at 12 hours had a good accuracy [AUROC=0.87 (95% CI: 0.81-0.93)] while its use in a multivariable model had an excellent accuracy both in derivation [AUROC=0.92 (95% CI: 0.89-0.95)] and internal validation [AUROC=0.91 (95% CI: 0.90-0.92)]. In critically ill children, the lung ultrasound score early after admission may predict prolonged invasive mechanical ventilation.

Quantitative susceptibility mapping at 7 T in COVID-19: brainstem effects and outcome associations.

Post-mortem studies have shown that patients dying from severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection frequently have pathological changes in their CNS, particularly in the brainstem. Many of these changes are proposed to result from para-infectious and/or post-infection immune responses. Clinical symptoms such as fatigue, breathlessness, and chest pain are frequently reported in post-hospitalized coronavirus disease 2019 (COVID-19) patients. We propose that these symptoms are in part due to damage to key neuromodulatory brainstem nuclei. While brainstem involvement has been demonstrated in the acute phase of the illness, the evidence of long-term brainstem change on MRI is inconclusive. We therefore used ultra-high field (7 T) quantitative susceptibility mapping (QSM) to test the hypothesis that brainstem abnormalities persist in post-COVID patients and that these are associated with persistence of key symptoms. We used 7 T QSM data from 30 patients, scanned 93-548 days after hospital admission for COVID-19 and compared them to 51 age-matched controls without prior history of COVID-19 infection. We correlated the patients' QSM signals with disease severity (duration of hospital admission and COVID-19 severity scale), inflammatory response during the acute illness (C-reactive protein, D-dimer and platelet levels), functional recovery (modified Rankin scale), depression (Patient Health Questionnaire-9) and anxiety (Generalized Anxiety Disorder-7). In COVID-19 survivors, the MR susceptibility increased in the medulla, pons and midbrain regions of the brainstem. Specifically, there was increased susceptibility in the inferior medullary reticular formation and the raphe pallidus and obscurus. In these regions, patients with higher tissue susceptibility had worse acute disease severity, higher acute inflammatory markers, and significantly worse functional recovery. This study contributes to understanding the long-term effects of COVID-19 and recovery. Using non-invasive ultra-high field 7 T MRI, we show evidence of brainstem pathophysiological changes associated with inflammatory processes in post-hospitalized COVID-19 survivors.

Post-COVID-19 condition in children: epidemiological evidence stratified by acute disease severity.

To determine the prevalence of pediatric Post-COVID-19 condition (PPCC), identify risk factors, and assess the quality of life in children with differing severities of acute COVID-19. During a prospective longitudinal study with a 1-year follow-up, we compared non-hospitalized (mild) and hospitalized (severe) COVID-19 cases to a negatively tested control group. 579 children were included in this study. Of these, 260 had mild acute disease (median age:8, IQR:6-10), 60 had severe acute disease (median age:1, IQR:0.1-4.0), and 259 tested negative for SARS-CoV-2 (NT) (median age:8, IQR:5-10). At three months, 14.6% of the SARS-CoV-2 positive mild group (RR:6.31 (CI 95%: 2.71-14.67)) and 29.2% of the severe group (RR:12.95 (CI 95%: 5.37-31.23)) reported sequelae, versus 2.3% of the NT group. PPCC prevalence in the mild group decreased from 16.1% at one month to 4.4% at one year. Children with PPCC exhibited lower physical health-related quality of life scores and higher fatigue scores than the NT children. Severe acute COVID-19 in children leads to a higher PPCC prevalence than in mild cases. PPCC prevalence decreases over time. Risk factors at three months include prior medical history, hospital admission, and persistent fatigue one month after a positive test. We demonstrate children with severe COVID-19 are more likely to develop Post-COVID-19 condition than those with mild or no infections, and highlights the risk factors. Here we have stratified by acute disease severity, prospectively included a negative control group, and have demonstrated the heterogeneity in prevalence when utilizing various recent definitions of post-COVID. Identifying risk factors for pediatric post-COVID and highlighting the heterogeneity in prevalence based on various current definitions for post-COVID should aid in correctly identifying potential pediatric post-COVID cases, aiding in early intervention.

Neutrophil activation, acute lung injury and disease severity in Plasmodium knowlesi malaria.

The risk of severe malaria from the zoonotic parasite Plasmodium knowlesi approximates that from P. falciparum. In severe falciparum malaria, neutrophil activation contributes to inflammatory pathogenesis, including acute lung injury. The role of neutrophil activation in the pathogenesis of severe knowlesi malaria has not been examined. We evaluated 213 patients with P. knowlesi mono-infection (138 non-severe, 75 severe) and 49 Plasmodium-negative controls from Malaysia. Markers of neutrophil activation (soluble neutrophil elastase [NE], citrullinated histone [CitH3] and circulating neutrophil extracellular traps [NETs]) were quantified in peripheral blood by microscopy and immunoassays. Findings were correlated with malaria severity, ALI clinical criteria, biomarkers of parasite biomass, haemolysis, and endothelial activation. Neutrophil activation increased with disease severity, with median levels higher in severe than non-severe malaria and controls for NE (380[IQR:210-930]ng/mL, 236[139-448]ng/mL, 218[134-307]ng/mL, respectively) and CitH3 (8.72[IQR:3.0-23.1]ng/mL, 4.29[1.46-9.49]ng/mL, 1.53[0.6-2.59]ng/mL, respectively)[all p<0.01]. NETs were higher in severe malaria compared to controls (126/μL[IQR:49-323] vs 51[20-75]/μL, p<0.001). In non-severe malaria, neutrophil activation fell significantly upon discharge from hospital (p<0.03). In severe disease, NETs, NE, and CitH3 were correlated with parasitaemia, cell-free haemoglobin and angiopoietin-2 (all Pearson's r>0.24, p<0.05). Plasma NE and angiopoietin-2 were higher in knowlesi patients with ALI than those without (p<0.008); neutrophilia was associated with an increased risk of ALI (aOR 3.27, p<0.01). In conclusion, neutrophil activation is increased in ALI and in proportion to disease severity in knowlesi malaria, is associated with endothelial activation, and may contribute to disease pathogenesis. Trials of adjunctive therapies to regulate neutrophil activation are warranted in severe knowlesi malaria.

Impact of interleukin 6 levels on acute lung injury risk and disease severity in critically ill sepsis patients.

Sepsis is a life-threatening condition characterized by a dysregulation of the host response to infection that can lead to acute lung injury (ALI) and multiple organ dysfunction syndrome (MODS). Interleukin 6 (IL-6) is a pro-inflammatory cytokine that plays a crucial role in the pathogenesis of sepsis and its complications. To investigate the relationship among plasma IL-6 levels, risk of ALI, and disease severity in critically ill patients with sepsis. This prospective and observational study was conducted in the intensive care unit of a tertiary care hospital between January 2021 and December 2022. A total of 83 septic patients were enrolled. Plasma IL-6 levels were measured upon admission using an enzyme-linked immunosorbent assay. The development of ALI and MODS was monitored during hospitalization. Disease severity was evaluated by Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA) scores. Among the 83 patients with sepsis, 38 (45.8%) developed ALI and 29 (34.9%) developed MODS. Plasma IL-6 levels were significantly higher in patients who developed ALI than in those without ALI (median: 125.6 pg/mL vs 48.3 pg/mL; P < 0.001). Similarly, patients with MODS had higher IL-6 levels than those without MODS (median: 142.9 pg/mL vs 58.7 pg/mL; P < 0.001). Plasma IL-6 levels were strongly and positively correlated with APACHE II (r = 0.72; P < 0.001) and SOFA scores (r = 0.68; P < 0.001). Elevated plasma IL-6 levels in critically ill patients with sepsis were associated with an increased risk of ALI and MODS. Higher IL-6 levels were correlated with greater disease severity, as reflected by higher APACHE II and SOFA scores. These findings suggest that IL-6 may serve as a biomarker for predicting the development of ALI and disease severity in patients with sepsis.

Clinical Associations of E148Q Heterozygosity: What to Expect From E148Q?

The exact effects of MEFV variants on inflammation are still under investigation, and reports on variants of unknown significance, particularly the E148Q variant, have been conflicting. Therefore, this study aims to investigate patients exhibiting E148Q heterozygosity, focusing on diagnoses and disease courses to assist physicians in interpreting the variant. Data of pediatric patients presenting to the Pediatric Rheumatology clinic between November 2016 and September 2023, exhibiting only E148Q heterozygosity in MEFV gene analysis, were extracted. Patients who were lost before 9 months of follow-up have been excluded to ensure the completion of initial diagnostic tests and evaluations. Among the 119 patients with E148Q variant, the diagnoses were as follows: healthy, 51.3%; IgA vasculitis, 10.1%; Familial Mediterranean Fever (FMF), 7.6%; Periodic fever, Aphtous stomatitis, Pharyngitis, Adenitis (PFAPA), 6.7%; and other diagnoses, 19.3%. IgA vasculitis patients experienced articular, gastrointestinal, and renal involvement at rates of 91.7%, 58.3%, and 16.7%, respectively. Complete response, partial response, and no response to colchicine were 37.5%, 12.5%, and 50%, respectively, in PFAPA patients. All FMF patients responded to colchicine treatment resulting in reduced mean FMF episode counts in 6 months from 3.22 ± 0.92 to 0.56 ± 0.52. The E148Q variant may amplify inflammation and modify disease courses. Patients with the E148Q variant experiencing typical FMF episodes should receive colchicine, but clinicians should exercise caution regarding alternative diagnoses. Additionally, the E148Q variant may increase acute phase reactants and disease severity in IgA vasculitis. However, to reach definitive conclusions on its treatment-modifying role in PFAPA, universal diagnosis and treatment response criteria should be adopted.

Quality of Sleep and Mental Symptoms Contribute to Health-Related Quality of Life after COVID-19 Pneumonia, a Follow-Up Study of More than 2 Years.

A follow-up study was designed to assess correlations among physical signs, quality of sleep, common mental symptoms, and health-related quality of life after moderate to severe COVID-19 pneumonia. Daily changes in dyspnoea and pulse oximetry were recorded (200 days), and four evaluations (in >2 years) were performed on quality of sleep, mental symptoms, cognitive performance, and health-related quality of life. In a single center, 72 adults participated in the study (52.5 ± 13.7 years old), with no psychiatry/neurology/chronic lung/infectious diseases, chronic use of corticosteroids/immunosuppressive therapy, or pregnancy. Daily agendas showed delayed decreases in dyspnoea scores compared to pulse oximetry and heart rate recordings; however, changes in pulse oximetry were minimal. Slight changes in cognitive performance were related to the general characteristics of the participants (obesity and tobacco use) and with the severity of acute disease (MANCOVA, p < 0.001). Health-related quality of life gradually improved (MANCOVA, p < 0.004). During recovery, bad quality of sleep and mental symptoms (mainly attention/concentration) contributed to the subscores on health perception and vitality in the health-related quality of life assessment. Early mental support services including sleep hygiene could be beneficial during rehabilitation after acute COVID-19.

Correlation between Acute Liver Injury and Disease Severity in Hospitalized Egyptian Patients with Covid-19

Abstract Background COVID-19 pandemic has brought new health threats and challenges to the world. However, the scientific progress over the last months has shed more light on several key questions concerning COVID-19-associated complications. Aim of the Work The aim of this study is to correlate acute liver injury in Covid-19 hospitalized patients with the severity of the disease. Patients and Methods This was a cross-sectional study that was conducted on 110 patients at Ain Shams University hospitals including Ain-Shams Quarantine field hospital, Ain Shams University Quarantine hospital in Al-Obour, and Quarantine ICU of Demerdash through twenty months. Results In total, 110 patients with positive SARS-CoV-2 PCR test were included in this study. The study population was mostly males with 58.2% and median age of the population was 65 years old. As regards to the morbidity status of the study population, 67.3% of the patient died due to disease severity, while 32.7% showed recovery. There was statistical significant relation between liver injury in terms of elevation of (AST-ALP-GGT-Bilirubin) and the increase in oxygen demand. As regards to the inflammatory markers, they significantly correlated with liver injury. Conclusion This study concluded that impaired liver function constitute a common finding in COVID-19 patients. Deterioration of liver function worsens the prognosis and prolongs duration of hospitalization. Thus, critically ill Covid-19 patients should be monitored closely to manage any possible complications.

Associations of tissue factor and tissue factor pathway inhibitor with organ dysfunctions in septic shock

Coagulopathy, microvascular alterations and concomitant organ dysfunctions are hallmarks of sepsis. Attempts to attenuate coagulation activation with an inhibitor of tissue factor (TF), i.e. tissue factor pathway inhibitor (TFPI), revealed no survival benefit in a heterogenous group of sepsis patients, but a potential survival benefit in patients with an international normalized ratio (INR) < 1.2. Since an increased TF/TFPI ratio determines the procoagulant activity specifically on microvascular endothelial cells in vitro, we investigated whether TF/TFPI ratio in blood is associated with INR alterations, organ dysfunctions, disseminated intravascular coagulation (DIC) and outcome in septic shock. Twenty-nine healthy controls (HC) and 89 patients with septic shock admitted to a tertiary ICU were analyzed. TF and TFPI in blood was analyzed and related to organ dysfunctions, DIC and mortality. Patients with septic shock had 1.6-fold higher levels of TF and 2.9-fold higher levels of TFPI than HC. TF/TFPI ratio was lower in septic shock compared to HC (0.003 (0.002–0.005) vs. 0.006 (0.005–0.008), p < 0.001). Non-survivors had higher TFPI levels compared to survivors (43038 (29354–54023) vs. 28041 (21675–46582) pg/ml, p = 0.011). High TFPI levels were associated with acute kidney injury, liver dysfunction, DIC and disease severity. There was a positive association between TF/TFPI ratio and troponin T (b = 0.531 (0.309–0.754), p < 0.001). A high TF/TFPI ratio is exclusively associated with myocardial injury but not with other organ dysfunctions. Systemic TFPI levels seem to reflect disease severity. These findings point towards a pathophysiologic role of TF/TFPI in sepsis-induced myocardial injury.

Alterations in microbiome associated with acute pancreatitis.

This review evaluates the current knowledge of gut microbiome alterations in acute pancreatitis, including those that can increase acute pancreatitis risk or worsen disease severity, and the mechanisms of gut microbiome driven injury in acute pancreatitis. Recent observational studies in humans showed the association of gut microbiome changes (decreased gut microbiome diversity, alterations in relative abundances of certain species, and association of unique species with functional pathways) with acute pancreatitis risk and severity. Furthermore, in-vivo studies highlighted the role of gut microbiome in the development and severity of acute pancreatitis using FMT models. The gut barrier integrity, immune cell homeostasis, and microbial metabolites appear to play key roles in acute pancreatitis risk and severity. Large human cohort studies that assess gut microbiome profile, its metabolites and impact on acute pancreatitis risk and severity will be crucial for development of innovative prediction, prevention and treatment strategies.

Analysis of mononuclear leukocyte functional activity in peripheral blood of patients with varying clinical severity of acute Lyme disease

The aim of the study is to assess spontaneous and phytohemagglutinin (PHA)-induced proliferative and cytokine secretory activity in mononuclear blood cell cultures of patients with acute Lyme borreliosis (LB) over times before and after antibiotic therapy as well as depending on clinical severity. Materials and methods. Activity of blast transformation reaction (BTR) of lymphocytes and the secretion levels of interleukins (IL)-1β, IL-2, IL-6, IL-4, IL-10, IL-8, tumor necrosis factor (TNF)-α, monocyte chemoattractant protein (MCP)-1, interferon (IFN)-γ and IFN-α were assessed twice over time in the cultures of mononuclear blood cells of 18 and 14 patients with mild and moderate severity of acute LB. Results. It was determined that the moderate clinical course of acute LB as compared with the mild course was associated with the significant suppression of BTR levels, the increases in spontaneous and/or PHA-stimulated production levels of proinflammatory cytokines IL-1β, IL-6, IL-8, TNF-α and MCP-1, which were balanced by the increases in secretion levels of anti-inflammatory cytokines IL-10 and IL-4. The initial suppression of IFN-γ secretion in this group gave way to an increase in its production over time, which generally corresponded to the formation of an immune response of the mixed Th1/Th2 type.

Recovery Dynamics and Prognosis After Dialysis for Acute Kidney Injury

The interplay among baseline kidney function, severity of acute kidney disease (AKD), and post-AKD kidney function has significant associations with patient outcomes. However, a comprehensive understanding of how these factors are collectively associated with mortality, major adverse cardiac events (MACEs), and end-stage kidney disease (ESKD) in patients with dialysis-requiring acute kidney injury (AKI-D) is yet to be fully explored. To investigate the associations of baseline kidney function, AKD severity, and post-AKD kidney function with mortality, MACEs, and ESKD in patients with AKI-D. This nationwide, population-based cohort study of patients with AKI-D was conducted between January 1, 2015, and December 31, 2018, using data from various health care settings included in the Taiwan nationwide population-based cohort database. Data analysis was conducted from April 28, 2022, to June 30, 2023. Exposure to severe AKI and baseline and post-AKD kidney function. The primary outcomes were all-cause mortality and incident MACEs, and secondary outcomes were risks of permanent dialysis and readmission. A total of 6703 of 22 232 patients (mean [SD] age, 68.0 [14.7] years; 3846 [57.4%] male) with AKI-D with post-AKD kidney function follow-up and AKD stage data were enrolled. During a mean (SD) 1.2 (0.9) years of follow-up, the all-cause mortality rate was 28.3% (n = 1899), while the incidence rates of MACEs and ESKD were 11.1% (n = 746) and 16.7% (n = 1119), respectively. After adjusting for known covariates, both post-AKD kidney function and baseline kidney function, but not AKD severity, were independently associated with all-cause mortality, MACEs, ESKD, and readmission. Moreover, worse post-AKD kidney function correlated with progressive and significant increases in the risk of adverse outcomes. In this cohort study of patients with AKI-D, more than one-quarter of patients died after 1.2 years of follow-up. Baseline and post-AKD kidney functions serve as important factors associated with the long-term prognosis of patients with AKI-D. Therefore, concerted efforts to understand the transition from post-AKD to chronic kidney disease are crucial.

Plasma steroid concentrations reflect acute disease severity and normalise during recovery in people hospitalised with COVID-19.

Endocrine systems are disrupted in acute illness, and symptoms reported following coronavirus disease 2019 (COVID-19) are similar to those found with clinical hormone deficiencies. We hypothesised that people with severe acute COVID-19 and with post-COVID symptoms have glucocorticoid and sex hormone deficiencies. Samples were obtained for analysis from two UK multicentre cohorts during hospitalisation with COVID-19 (International Severe Acute Respiratory Infection Consortium/World Health Organisation [WHO] Clinical Characterization Protocol for Severe Emerging Infections in the UK study), and at follow-up 5 months after hospitalisation (Post-hospitalisation COVID-19 study). Plasma steroids were quantified by liquid chromatography-mass spectrometry. Steroid concentrations were compared against disease severity (WHO ordinal scale) and validated symptom scores. Data are presented as geometric mean (SD). In the acute cohort (n = 239, 66.5% male), plasma cortisol concentration increased with disease severity (cortisol 753.3 [1.6] vs. 429.2 [1.7] nmol/L in fatal vs. least severe, p < .001). In males, testosterone concentrations decreased with severity (testosterone 1.2 [2.2] vs. 6.9 [1.9] nmol/L in fatal vs. least severe, p < .001). In the follow-up cohort (n = 198, 62.1% male, 68.9% ongoing symptoms, 165 [121-192] days postdischarge), plasma cortisol concentrations (275.6 [1.5] nmol/L) did not differ with in-hospital severity, perception of recovery, or patient-reported symptoms. Male testosterone concentrations (12.6 [1.5] nmol/L) were not related to in-hospital severity, perception of recovery or symptom scores. Circulating glucocorticoids in patients hospitalised with COVID-19 reflect acute illness, with a marked rise in cortisol and fall in male testosterone. These findings are not observed 5 months from discharge. The lack of association between hormone concentrations and common post-COVID symptoms suggests steroid insufficiency does not play a causal role in this condition.

Accelarated immune ageing is associated with COVID-19 disease severity

BackgroundThe striking increase in COVID-19 severity in older adults provides a clear example of immunesenescence, the age-related remodelling of the immune system. To better characterise the association between convalescent immunesenescence and acute disease severity, we determined the immune phenotype of COVID-19 survivors and non-infected controls.ResultsWe performed detailed immune phenotyping of peripheral blood mononuclear cells isolated from 103 COVID-19 survivors 3–5 months post recovery who were classified as having had severe (n = 56; age 53.12 ± 11.30 years), moderate (n = 32; age 52.28 ± 11.43 years) or mild (n = 15; age 49.67 ± 7.30 years) disease and compared with age and sex-matched healthy adults (n = 59; age 50.49 ± 10.68 years). We assessed a broad range of immune cell phenotypes to generate a composite score, IMM-AGE, to determine the degree of immune senescence. We found increased immunesenescence features in severe COVID-19 survivors compared to controls including: a reduced frequency and number of naïve CD4 and CD8 T cells (p < 0.0001); increased frequency of EMRA CD4 (p < 0.003) and CD8 T cells (p < 0.001); a higher frequency (p < 0.0001) and absolute numbers (p < 0.001) of CD28−ve CD57+ve senescent CD4 and CD8 T cells; higher frequency (p < 0.003) and absolute numbers (p < 0.02) of PD-1 expressing exhausted CD8 T cells; a two-fold increase in Th17 polarisation (p < 0.0001); higher frequency of memory B cells (p < 0.001) and increased frequency (p < 0.0001) and numbers (p < 0.001) of CD57+ve senescent NK cells. As a result, the IMM-AGE score was significantly higher in severe COVID-19 survivors than in controls (p < 0.001). Few differences were seen for those with moderate disease and none for mild disease. Regression analysis revealed the only pre-existing variable influencing the IMM-AGE score was South Asian ethnicity (β\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\beta$$\\end{document} = 0.174, p = 0.043), with a major influence being disease severity (β\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\beta$$\\end{document} = 0.188, p = 0.01). ConclusionsOur analyses reveal a state of enhanced immune ageing in survivors of severe COVID-19 and suggest this could be related to SARS-Cov-2 infection. Our data support the rationale for trials of anti-immune ageing interventions for improving clinical outcomes in these patients with severe disease.

Physical activity, acute severity and long-term consequences of COVID-19: an 18-month follow-up survey based on a Swedish national cohort

ObjectiveTo investigate how changes in levels of physical activity (PA) in regard to acute disease severity relate to perceived difficulties in performing daily life activities 18 months after COVID-19 infection.DesignAn...

Global cardiovascular risk, COVID-19 severity and post-COVID-19 syndrome: a clinical study.

Post-COVID-19 is a syndrome defined by signs and symptoms present until 12 weeks after COVID-19, lasting for more than 8 weeks, not explained by an alternative diagnosis. The present study aimed to assess whether the cardiovascular risk (CVR) of patients with COVID-19 correlates with symptoms and changes in respiratory function parameters in post-COVID-19. The association between CVR and the severity of acute disease was also considered. Between 21/04/21-01/09/21, we enrolled 1,782 consecutive patients with COVID-19. We divided these subjects into (i) 4 levels, based on the severity of COVID-19 (home care; hospitalized/no oxygen therapy; hospitalized/oxygen therapy; hospitalized/NIV-ICU), (ii) 2 levels, according to CVR calculated with the European Society of Cardiology SCORE tables (low-intermediate risk; high or very high risk). All subjects underwent a 3-month follow-up considering post-COVID-19 symptoms. In post-COVID-19 patients, high or very-high CVR was associated with (i) increased risk of hospitalization for COVID-19 (p<0.0001), (ii) higher prevalence of severe clinical manifestations and ICU admission (p<0.0001), (iii) development of post-COVID-19 (p<0.0001) and (iv) increased risk of a larger post-COVID-19 burden of disease. We found a statistically significant association between CVR, severity of COVID-19, and post-COVID-19 syndrome three months after the end of acute disease.

A Multi-Center Study Investigating Long COVID-19 in Healthcare Workers from North-Eastern Italy: Prevalence, Risk Factors and the Impact of Pre-Existing Humoral Immunity-ORCHESTRA Project.

Introduction: The impact of long-COVID-19 syndrome is rather variable, since it is influenced by several residual confounders. This study aimed to investigate the prevalence of long COVID-19 in healthcare workers (HCWs) from four university hospitals in north-eastern Italy: Trieste, Padua, Verona, and Modena-Reggio Emilia. Methods: During the period June 2022-August 2022, HCWs were surveyed for past COVID-19 infections, medical history, and any acute as well as post-COVID-19 symptoms. The prevalence of long COVID-19 was estimated at 30-60 days or 61+ days since first negative swab following first and second COVID-19 episode. Furthermore, the risk of long COVID-19 was investigated by multivariable logistic regression. Results were expressed as the adjusted odds ratio (aOR) with a 95% confidence interval (95%CI). Results: 5432 HCWs returned a usable questionnaire: 2401 were infected with SARS-CoV-2 at least once, 230 were infected at least twice, and 8 were infected three times. The prevalence of long COVID-19 after a primary COVID-19 infection was 24.0% at 30-60 days versus 16.3% at 61+ days, and 10.5% against 5.5% after the second SARS-CoV-2 event. The most frequent symptoms after a first COVID-19 event were asthenia (30.3%), followed by myalgia (13.7%), cough (12.4%), dyspnea (10.2%), concentration deficit (8.1%), headache (7.3%), and anosmia (6.5%), in decreasing order of prevalence. The risk of long COVID-19 at 30-60 days was significantly higher in HCWs hospitalized for COVID-19 (aOR = 3.34; 95%CI: 1.62; 6.89), those infected with SARS-CoV-2 during the early pandemic waves-namely the Wuhan (aOR = 2.16; 95%CI: 1.14; 4.09) or Alpha (aOR= 2.05; 95%CI: 1.25; 3.38) transmission periods-and progressively increasing with viral shedding time (VST), especially 15+ days (aOR = 3.20; 95%CI: 2.07; 4.94). Further determinants of long COVID-19 at 30-60 days since primary COVID-19 event were female sex (aOR = 1.91; 95%CI: 1.30; 2.80), age >40 years, abnormal BMI, or administrative services (reference category). In contrast, HCWs vaccinated with two doses before their primary infection (aOR = 0.57; 95%CI: 0.34; 0.94), undergraduate students, or postgraduate medical trainees were less likely to experience long COVID-19 at 30-60 days. Apart from pandemic waves, the main determinants of long COVID-19 at 30-60 days were confirmed at 61+ days. Conclusions: The risk of long COVID-19 following primary infection increased with the severity of acute disease and VST, especially during the initial pandemic waves, when more virulent viral strains were circulating, and susceptibility to SARS-CoV-2 was higher since most HCWs had not been infected yet, COVID-19 vaccines were still not available, and/or vaccination coverage was still building up. The risk of long COVID-19 therefore decreased inversely with humoral immunity at the individual level. Nevertheless, the prevalence of long COVID-19 was remarkably lower after SARS-CoV-2 reinfections regardless of vaccination status, suggesting that hybrid humoral immunity did not increase protection against the syndrome compared to immunity mounted by either natural infection or vaccination separately. Since the risk of long COVID-19 is currently low with Omicron and patients who developed the syndrome following SARS-CoV-2 infection in the early pandemic waves tend to return to a state of full health with time, a cost-effective approach to screen post-COVID-19 symptoms during the Omicron time could be restricted to vulnerable individuals developing severe disease and/or with prolonged VST.

Patient experiences with SARS-CoV-2: Associations between patient experience of disease and coping profiles.

Severe acute respiratory syndrome coronavirus 2, (SARS-CoV-2,) caused an influx of patients with acute disease characterized by a variety of symptoms termed COVID-19 disease, with some patients going on to develop post-acute COVID-19 syndrome. Individual factors like sex or coping styles are associated with a person's disease experience and quality of life. Individual differences in coping styles used to manage COVID-19 related stress correlate with physical and mental health outcomes. Our study sought to understand the relationship between COVID-19 symptoms, severity of acute disease, and coping profiles. An online survey to assess symptoms, functional status, and recovery in a large group of patients was nationally distributed online. The survey asked about symptoms, course of illness, and included the Brief-COPE and the adapted Social Relationship Inventory. We used descriptive and cluster analyses to characterize patterns of survey responses. 976 patients were included in the analysis. The most common symptoms reported by the patients were fatigue (72%), cough (71%), body aches/joint pain (66%), headache (62%), and fever/chills (62%). 284 participants reported PACS. We described three different coping profiles: outward, inward, and dynamic copers. Fatigue, cough, and body aches/joint pains were the most frequently reported symptoms. PACS patients were sicker, more likely to have been hospitalized. Of the three coping profiles, outward copers were more likely to be admitted to the hospital and had the healthiest coping strategies. Dynamic copers activated several coping strategies both positive and negative; they were also younger and more likely to report PACS. Cough, fatigue, and body aches/joint pain are common and most important to patients with acute COVID-19, while shortness of breath defined the experience for patients with PACS. Of the three coping profiles, dynamic copers were more likely to report PACS. Additional investigations into coping profiles in general, and the experience of COVID-19 and PACS is needed.