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 to inflammation, severe respiratory failure and mortality in hospitalized men and women with coronavirus disease 2019 (COVID-19) and compare these to hormone concentrations in hospitalized patients with bacterial community-acquired pneumonia (CAP), 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 three days of admission. Associations were assessed by logistic regression analysis in patients with COVID-19, and results were reported as odds ratio with 95% confidence interval per two-fold reduction after adjustment for age, comorbidities, days to sample collection, and IL-6 concentrations. RESULTS: In total 278 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 higher odds of mechanical 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 predicted severe respiratory failure in women with COVID-19.

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.

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.

Silent hypoxia in patients with SARS CoV-2 infection before hospital discharge.

OBJECTIVE: To assess the degree of hypoxia and subjective dyspnea elicited by a 6-minute walking test (6MWT) in COVID-19 patients prior to discharge. METHODS: A 6MWT was performed in 26 discharge-ready COVID-19 patients without chronic pulmonary disease or cardiac failure. Heart rate, oxyhemoglobin saturation (SpO2), respiratory rate, and subjective dyspnea measured on the Borg CR-10 scale were measured before and immediately after the 6MWT, with continuous monitoring of SpO2 and heart rate during the 6MWT. The 6MWT was terminated if SpO2 dropped below 90%. A historical cohort of 204 patients with idiopathic pulmonary fibrosis (IPF) was used for comparison. RESULTS: 13 (50%) of the COVID-19 patients developed exercise-induced hypoxia (SpO2 < 90%) during the 6MWT, of which one third had pulmonary embolism. COVID-19 patients experienced less hypoxia-related dyspnea during the 6MWT compared with patients with IPF. CONCLUSION: The 6MWT is a potential tool in the diagnosis of asymptomatic exercise-induced hypoxia in hospitalized COVID-19 patients prior to discharge. Due to important methodological limitations, further studies are needed to confirm our findings and to investigate their clinical consequences.