Adiponectin as a predictor of mortality and readmission in patients with community-acquired pneumonia: a prospective cohort study.

Background: Adiponectin is secreted by adipocytes and is inversely associated with obesity. Given the association between low body mass index (BMI) and higher mortality risk after community-acquired pneumonia (CAP), we hypothesized that high adiponectin levels are associated with a higher risk of adverse clinical outcomes in patients with CAP. Methods: In a prospective cohort study of 502 patients hospitalized with CAP, adiponectin was measured in serum at admission. The associations between adiponectin and clinical outcomes were estimated with logistic regression analyses adjusted for age, sex, and measures of obesity (BMI, waist circumference or body fat percentage). Results: Adiponectin was associated with higher 90-day mortality for each 1 µg/mL increase [OR 1.02, 95% CI (1.00, 1.04), p = 0.048] independent of age and sex. Likewise, adiponectin was associated with a higher risk of 90-day readmission for each 1 µg/mL increase [OR 1.02, 95% CI (1.01, 1.04), p = 0.007] independent of age and sex. The association between adiponectin and 90-day mortality disappeared, while the association with 90-day readmission remained after adjusting for adiposity. Conclusion: Adiponectin was positively associated with mortality and readmission. The association with mortality depended on low body fat, whereas the association with readmission risk was independent of obesity.

Effect of Exercise Training on Prognosis in Community-Acquired Pneumonia: A Randomised Controlled Trial.

OBJECTIVE: To investigate the effect of standard care (SoC) combined with supervised in-bed cycling (Bed-Cycle) or booklet exercises (Book-Exe) versus SoC in community-acquired pneumonia (CAP). METHODS: In this randomised controlled trial, 186 patients with CAP were assigned to SoC (n = 62), Bed-Cycle (n = 61), or Book-Exe (n = 63). Primary outcome length of stay (LOS) was analysed with analysis of covariance. Secondary outcomes, 90-day readmission and 180-day mortality, were analysed with Cox proportional hazard regression and readmission days with negative-binominal regression. RESULTS: LOS was -2% (95% CI -24 to 25%) and -1% (95% CI -22 to 27%) for Bed-Cycle and Book-Exe, compared to SoC. 90-day readmission was 35.6% for SoC, 27.6% for Bed-Cycle, and 21.3% for Book-Exe. Adjusted hazard ratio (aHR) for 90-day readmission was 0.63 (95% CI 0.33-1.21) and 0.54 (95% CI 0.27-1.08) for Bed-Cycle and Book-Exe compared to SoC. aHR for 90-day readmission for combined exercise was 0.59 (95% CI 0.33-1.03) compared to SoC. aHR for 180-day mortality was 0.84 (95% CI 0.27-2.60) and 0.82 (95% CI 0.26-2.55) for Bed-Cycle and Book-Exe compared to SoC. Number of readmission days was 226 for SoC, 161 for Bed-Cycle, and 179 for Book-Exe. Incidence rate ratio for readmission days was 0.73 (95% CI 0.48-1.10) and 0.77 (95% CI 0.51-1.15) for Bed-Cycle and Book-Exe compared to SoC. CONCLUSION: Although supervised exercise training during admission with CAP did not reduce LOS or mortality, this trial suggests its potential to reduce readmission risk and number of readmission days.

Opportunistic non-communicable diseases in times of COVID-19.

We previously proposed the term 'opportunistic non-communicable diseases (NCDs)' to raise awareness of how NCDs thrive in societies with inadequate healthcare services. However, we did not anticipate that within the next year the new coronavirus disease (COVID-19) would sweep the globe. Lockdowns became the primary strategy for mitigation in most countries. However, the extensive restrictions and allocation of resources towards the containment of the pandemic have likely served as a catalyst of NCDs, especially in populations, societies and individuals already at high risk. We are presenting evidence to qualify two primary factors responsible for the potential impact on the development of NCDs during the COVID-19 pandemic. The first is disrupted healthcare services including avoidance and postponement of healthcare visits. The second is effects of changing lifestyle and living conditions including isolation, loss of job and income. The accumulated effect of these factors will likely further accelerate the development of NCDs and impair their management, especially in low- and middle-income countries. Insufficient vaccination coverage due to inequality in vaccine distribution and vaccine hesitancy left room for the incubation of immune-evasive variants that threatened to sustain or reinitiate the pandemic. We believe the concept of opportunistic NCDs and the potential catalytic effect that pandemics may have on the development of NCDs and their management, should be used as further arguments to secure equal vaccine distribution, promote global vaccine acceptance and to speed up and increase investments in primary health care in low- and middle-income countries to cope with the already existing NCD crisis and to prepare for future epidemics.

Pituitary-gonadal hormones associated with respiratory failure in men and women hospitalized with COVID-19: an observational cohort study.

Aim: To explore pituitary-gonadal hormone concentrations and assess their association with inflammation, severe respiratory failure, and mortality in hospitalized men and women with COVID-19, and compare these to hormone concentrations in hospitalized patients with bacterial community-acquired pneumonia (CAP) and influenza virus CAP and to concentrations in a reference group of healthy individuals. Methods: Serum concentrations of testosterone, estrone sulfate, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and interleukin-6 (IL-6) were measured within 4 days of admission. Associations were assessed by logistic regression analysis in patients with COVID-19, and results were reported as odds ratio with 95% CI per two-fold reduction after adjustment for age, comorbidities, days to sample collection, and IL-6 concentrations. Results: In total, 278 patients with COVID-19, 21 with influenza virus CAP, and 76 with bacterial CAP were included. Testosterone concentrations were suppressed in men hospitalized with COVID-19, bacterial and influenza virus CAP, and moderately suppressed in women. Reductions in testosterone (OR: 3.43 (1.14-10.30), P = 0.028) and LH (OR: 2.51 (1.28-4.92), P = 0.008) were associated with higher odds of mehanical ventilation (MV) in men with COVID-19. In women with COVID-19, reductions in LH (OR: 3.34 (1.02-10-90), P = 0.046) and FSH (OR: 2.52 (1.01-6.27), P = 0.047) were associated with higher odds of MV. Conclusion: Low testosterone and LH concentrations were predictive of severe respiratory failure in men with COVID-19, whereas low concentrations of LH and FSH were predictive of severe respiratory failure in women with COVID-19.

Diabetes Status, c-Reactive Protein, and Insulin Resistance in Community-Acquired Pneumonia-A Prospective Cohort Study.

C-reactive protein (CRP) is commonly used to guide community-acquired pneumonia (CAP) treatment. A positive association between admission glucose and CRP levels has been observed in patients with CAP. The associations between prediabetes, unknown diabetes, acute-on-chronic hyperglycaemia, and CRP levels, and between admission CRP levels and insulin resistance (IR) in CAP, remain unexplored. This study investigated the associations firstly between chronic, acute, and acute-on-chronic hyperglycaemia and CRP levels, and secondly between admission CRP levels and IR in CAP. In a prospective cohort study of adults with CAP, the associations between chronic, acute, and acute-on-chronic hyperglycaemia (admission glucose minus HbA1c-derived average glucose) and CRP levels until admission day 3 were modelled with repeated-measures linear mixed models. IR was estimated with the homeostasis model assessment of IR (HOMA-IR). The association between admission CRP levels and HOMA-IR was modelled with linear regression. In 540 patients, no association between chronic, acute, or acute-on-chronic hyperglycaemia and CRP levels was found. In 266 patients, every 50 mg/L increase in admission CRP was associated with a 7% (95% CI 1-14%) higher HOMA-IR. In conclusion, our findings imply that hyperglycaemia does not influence CRP levels in patients with CAP, although admission CRP levels were positively associated with IR.

Association between Barthel Index, Grip Strength, and Physical Activity Level at Admission and Prognosis in Community-Acquired Pneumonia: A Prospective Cohort Study.

Background: Impaired functional status is a risk factor for hospitalization in patients with community-acquired pneumonia (CAP). The aim was to determine the influence of functional status and physical activity level on severe outcomes, including length of stay, admission to the intensive care unit (ICU), readmission, and mortality in patients with CAP. Methods: A prospective cohort study among patients hospitalized with CAP. Functional status was assessed with the Barthel index and grip strength, and physical activity level was assessed using the international physical activity questionnaire. Linear regression was used to assess the association with length of stay, and logistic regression was used to assess the risk of severe outcomes. Results: Among 355 patients admitted with CAP, 18% had a low Barthel index (<80), 45% had a low grip strength, and 75% had a low physical activity level. Low Barthel index was associated with increased risk of ICU admission (OR 3.6, 95% CI 1.2−10.9), longer length of stay (27.9%, 95% CI 2.3−59.7%), readmission within 30, 90, and 180 days (OR 2.1−2.4, p < 0.05), and mortality within 90 and 180 days (OR 4.2−5.0, p < 0.05). Low grip strength was associated with increased risk of 90 days readmission (OR 1.6, 95% CI 1.0−2.6, p < 0.05) and mortality within 30, 90, and 180 days (OR 2.6−3.2, p < 0.05). Low physical activity level was associated with increased risk of readmission within 90 and 180 days (OR 1.8−2.1, p < 0.05) and mortality within 30, 90, and 180 days (OR 3.3−5.5, p < 0.05). Conclusions: Impaired functional status and low physical activity level were associated with a longer length of stay and increased risk of ICU admission, readmission, and mortality in patients hospitalized with CAP. Routine assessment of functional status and physical activity level in clinical care could enable early identification of individuals with excess risk for a poor prognosis. Trial registration: ClinicalTrials.gov, NCT03795662.

Physical Inactivity and Sedentarism during and after Admission with Community-Acquired Pneumonia and the Risk of Readmission and Mortality: A Prospective Cohort Study.

BACKGROUND: Bed rest with limited physical activity is common during admission. The aim was to determine the association between daily step count and physical activity levels during and after admission with community-acquired pneumonia (CAP) and the risk of readmission and mortality. METHODS: A prospective cohort study of 166 patients admitted with CAP. Step count and physical activity were assessed with accelerometers during and after admission and were categorised as sedentary, light, or moderate-vigorous physical activity. Linear regression was used to assess the association between step count and length of stay. Logistic regression was used to assess the association between step count, physical activity level, and risk of readmission and mortality. RESULTS: Patients admitted with CAP were sedentary, light physically active, and moderate-to-vigorous physically active 96.4%, 2.6%, and 0.9% of their time, respectively, with 1356 steps/d. For every 500-step increase in daily step count on day 1, the length of stay was reduced by 6.6%. For every 500-step increase in daily step count during admission, in-hospital and 30-day mortality was reduced. Increased light and moderate-to-vigorous physical activity during admission were associated with reduced risk of in-hospital and 30-day mortality. After discharge, patients increased their daily step count to 2654 steps/d and spent more time performing light and moderate-to-vigorous physical activity. For every 500-step increase in daily step count after discharge, the risk of readmission was reduced. Higher moderate-to-vigorous physical activity after discharge was associated with a reduced risk of readmission. CONCLUSIONS: Increased physical activity during admission was associated with a reduced length of stay and risk of mortality, whereas increased physical activity after discharge was associated with a reduced risk of readmission in patients with CAP. Interventions focusing on increasing physical activity levels should be prioritised to improve the prognosis of patients admitted with CAP.

Biomarkers for iron metabolism among patients hospitalized with community-acquired pneumonia caused by infection with SARS-CoV-2, bacteria, and influenza.

Ferritin, the central iron storage protein, has attracted attention as a biomarker of severe COVID-19. Few studies have investigated regulators of iron metabolism in the context of COVID-19. The aim was to evaluate biomarkers for iron metabolism in the acute phase response to community-acquired pneumonia (CAP) caused by SARS-CoV-2 compared with CAP caused by bacteria or influenza virus in hospitalized patients. A cross-sectional study of 164 patients from the Surviving Pneumonia Cohort recruited between January 8, 2019 and May 26, 2020. Blood samples were collected at admission and analyzed for levels of C-reactive protein (CRP), ferritin, soluble transferrin receptor, erythroferrone, and hepcidin. Median (IQR) hepcidin was higher in SARS-CoV-2 with 143.8 (100.7-180.7) ng/mL compared with bacterial and influenza infection with 78.8 (40.1-125.4) and 53.5 (25.2-125.8) ng/mL, respectively. The median ferritin level was more than 2-fold higher in patients with SARS-CoV-2 compared with the other etiologies (p < 0.001). Patients with SARS-CoV-2 had lower levels of erythroferrone and CRP compared with those infected with bacteria. Higher levels of hepcidin and lower levels of erythroferrone despite lower CRP levels among patients with SARS-CoV-2 compared with those infected with bacteria indicate alterations in iron metabolism in patients with SARS-CoV-2 infection.

Risk factors for fatigue and impaired function eight months after hospital admission with COVID-19.

INTRODUCTION: We aimed to evaluate post-COVID-19 fatigue, change in functional capacity and health-related quality of life (HRQoL) eight months after discharge from hospital due to COVID-19. METHODS: A total of 83 patients (35 women) admitted to the Copenhagen University Hospital - North Zealand Hospital, Denmark, for COVID-19 during the period from March to June 2020 were evaluated eight months after discharge using validated questionnaires quantifying fatigue, HRQoL and post-COVID-19 functional status. Follow-up data were correlated with measures of pre-COVID-19 status (anthropometrics, comorbidities) and measures of severity of the acute infection. RESULTS: A total of 22 (65%) women and 12 (26%) men reported excessive fatigue. In all, 20 women (67%) and 17 men (37%) reported decreased physical function. Female sex was associated with fatigue. Loss of physical function was associated with pre-COVID-19 presence of heart disease and absence of lung disease. Severity of the acute COVID-19 infection was not associated with fatigue or change in functional status. Fatigue and functional status were correlated with both generic HRQoL and lung disease-specific HRQoL. CONCLUSIONS: Female sex was associated with a higher risk of fatigue eight months after hospitalisation with COVID-19 infection. Regarding loss of functional capacity after COVID-19, we found an apparently protective effect of pre-COVID-19 lung disease. Our findings underscore the urgent need for further research and the importance of evaluating those recovering from COVID-19 for symptoms of excessive fatigue and change in functional capacity irrespective of the severity of the initial infection. FUNDING: none. TRIAL REGISTRATION: not relevant.

Body composition, physical capacity, and immuno-metabolic profile in community-acquired pneumonia caused by COVID-19, influenza, and bacteria: a prospective cohort study.

BACKGROUND: Different pathogens can cause community-acquired pneumonia (CAP); however, the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) has re-emphasized the vital role of respiratory viruses as a cause of CAP. The aim was to explore differences in metabolic profile, body composition, physical capacity, and inflammation between patients hospitalized with CAP caused by different etiology. METHODS: A prospective study of Danish patients hospitalized with CAP caused by SARS-CoV-2, influenza, or bacteria. Fat (FM) and fat-free mass (FFM) were assessed with bioelectrical impedance analysis. Physical activity and capacity were assessed using questionnaires and handgrip strength. Plasma (p)-glucose, p-lipids, hemoglobin A1c (HbA1c), p-adiponectin, and cytokines were measured. RESULTS: Among 164 patients with CAP, etiology did not affect admission levels of glucose, HbA1c, adiponectin, or lipids. Overall, 15.2% had known diabetes, 6.1% had undiagnosed diabetes, 51.3% had pre-diabetes, 81% had hyperglycemia, and 60% had low HDL-cholesterol, with no difference between groups. Body mass index, FM, and FFM were similar between groups, with 73% of the patients being characterized with abdominal obesity, although waist circumference was lower in patients with COVID-19. Physical capacity was similar between groups. More than 80% had low handgrip strength and low physical activity levels. Compared to patients with influenza, patients with COVID-19 had increased levels of interferon (IFN)-γ (mean difference (MD) 4.14; 95% CI 1.36-12.58; p = 0.008), interleukin (IL)-4 (MD 1.82; 95% CI 1.12-2.97; p = 0.012), IL-5 (MD 2.22; 95% CI 1.09-4.52; p = 0.024), and IL-6 (MD 2.41; 95% CI 1.02-5.68; p = 0.044) and increased IFN-γ (MD 6.10; 95% CI 2.53-14.71; p < 0.001) and IL-10 (MD 2.68; 95% CI 1.53-4.69; p < 0.001) compared to patients with bacterial CAP, but no difference in IL-1ß, tumor necrosis factor-α, IL-8, IL-18, IL-12p70, C-reactive protein, and adiponectin. CONCLUSION: Despite higher inflammatory response in patients with COVID-19, metabolic profile, body composition, and physical capacity were similar to patients with influenza and bacterial CAP.

The impact of physical training on length of hospital stay and physical function in patients hospitalized with community-acquired pneumonia: protocol for a randomized controlled trial.

BACKGROUND: Community-acquired pneumonia (CAP) is a leading cause of hospitalization worldwide. Bed rest with low levels of physical activity is common during periods of hospitalization and leads to functional decline as well as increased risk of complications. The aim of this study is to assess the effect of supervised physical training during hospitalization with CAP compared with standard usual care for CAP on length of hospital stay, risk of readmission, mortality risk, physical capacity, muscle and fat mass, muscle strength, metabolic function, systemic inflammation, health-related quality of life, and physical activity level. METHODS: This study is a randomized controlled trial with three parallel experimental arms. Based on a sample size calculation, a total of 210 patients admitted with CAP at Nordsjællands Hospital, Hillerød, Denmark, will be recruited. Patients will be randomly allocated (1:1:1) to either (1) standard usual care, (2) standard usual care combined with in-bed cycling, or (3) standard usual care combined with exercises from a booklet. The primary outcome is differences in length of hospital stay between groups, with secondary outcomes being differences between groups in time to (1) 90-day readmission and (2) 180-day mortality. Further secondary outcomes are differences in changes from baseline between groups in (3) lean mass, (4) fat mass, (5) fat-free mass, (6) physical capacity, (7) health-related quality of life, (8) systemic inflammation, and (9) physical activity level after discharge. Data on length of hospital stay, readmission, and mortality will be collected from patient files, while total lean, fat, and fat-free mass will be quantitated by dual-energy x-ray absorptiometry and bioelectrical impedance analysis. Physical function will be assessed using grip strength, 30-s chair stand tests, and Barthel Index-100. Health-related quality of life will be assessed with the EQ-5D-5L questionnaire. Systemic inflammation will be assessed in blood samples, while accelerometers are used for measuring physical activity. DISCUSSION: If a simple physical training program appears to diminish the impact of critical illness and hospitalization on clinical outcome, mobility, and health-related quality of life, it may lead to novel therapeutic approaches in the treatment of patients hospitalized with CAP. TRIAL REGISTRATION: ClinicalTrials.gov NCT04094636 . Registered on 1 April 2019.