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.

High titers of neutralizing SARS-CoV-2 antibodies six months after symptom onset are associated with increased severity in COVID-19 hospitalized patients.

BACKGROUND: Viral shedding and neutralizing antibody (NAb) dynamics among patients hospitalized with severe coronavirus disease 2019 (COVID-19) and immune correlates of protection have been key questions throughout the pandemic. We investigated the duration of reverse transcriptase-polymerase chain reaction (RT-PCR) positivity, infectious viral shedding and NAb titers as well as the association between NAb titers and disease severity in hospitalized COVID-19 patients in Denmark 2020-2021. MATERIALS AND METHODS: Prospective single-center observational cohort study of 47 hospitalized COVID-19 patients. Oropharyngeal swabs were collected at eight time points during the initial 30 days of inclusion. Serum samples were collected after a median time of 7 (IQR 5 - 10), 37 (IQR 35 - 38), 97 (IQR 95 - 100), and 187 (IQR 185 - 190) days after symptom onset. NAb titers were determined by an in-house live virus microneutralization assay. Viral culturing was performed in Vero E6 cells. RESULTS: Patients with high disease severity had higher mean log2 NAb titers at day 37 (1.58, 95% CI [0.34 -2.81]), 97 (2.07, 95% CI [0.53-3.62]) and 187 (2.49, 95% CI [0.20- 4.78]) after symptom onset, compared to patients with low disease severity. Peak viral load (0.072, 95% CI [- 0.627 - 0.728]), expressed as log10 SARS-CoV-2 copies/ml, was not associated with disease severity. Virus cultivation attempts were unsuccessful in almost all (60/61) oropharyngeal samples collected shortly after hospital admission. CONCLUSIONS: We document an association between high disease severity and high mean NAb titers at days 37, 97 and 187 after symptom onset. However, peak viral load during admission was not associated with disease severity. TRIAL REGISTRATION: The study is registered at https://clinicaltrials.gov/ (NCT05274373).

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.

Telemetric Continuous Glucose Monitoring During the COVID-19 Pandemic in Isolated Hospitalized Patients in Denmark: A Randomized Controlled Exploratory Trial.

Objective: To investigate whether telemetric continuous glucose monitoring (CGM) in hospitalized and isolated patients with diabetes mellitus and coronavirus disease 2019 (COVID-19) is associated with better glycemic outcomes and fewer patient health care worker contacts compared to blood glucose monitoring by traditional point-of-care (POC) glucose testing and to investigate the user aspect of implementing a CGM-system in-hospital. Materials and Methods: A randomized controlled exploratory trial was performed on hospitalized and isolated patients with diabetes and COVID-19 from May 2020 until February 2021 at Nordsjællands Hospital, Denmark. Participants were randomized to nonblinded telemetric CGM (as the only glucose monitoring method) or traditional POC glucose testing + blinded CGM. The primary endpoint was time in range (TIR) based on CGM data in both groups. A questionnaire about the user aspect of the CGM system was answered by health care personnel (HCP). Results: We included 64 participants in the analysis, 31 in the CGM group and 33 in the POC glucose group. TIR median was 46% for the CGM group and 68% for the POC glucose group (P = 0.368). The mean glucose value for the CGM group was 11.1 and 10.8 mmol/L in the POC glucose group (P = 0.372). CGM was associated with fewer POC glucose measurements (P < 0.001). Out of 30 HCPs, 28 preferred telemetric CGM over POC glucose testing. Conclusion: Remote glucose monitoring by CGM did not improve glycemic outcomes compared to traditional POC glucose testing, but was associated with fewer patient-personnel contacts, saving time for HCPs performing diabetes-related tasks. Most HCPs preferred CGM. The study is registered at http://www.clinicaltrials.gov (#NCT04430608).