Circulating Adiponectin Levels Are Inversely Associated with Mortality and Respiratory Failure in Patients Hospitalized with COVID-19.

Background: Chronic low-grade inflammation associated with a dysregulated adipose tissue might contribute to amplifying the inflammatory response in severe COVID-19. The aim of this study was to examine the association between levels of circulating leptin and adiponectin and the severity and mortality of COVID-19. Methods: Serum levels of leptin and adiponectin were determined at admission in 123 individuals with confirmed COVID-19 and their association with 90-day mortality and respiratory failure was analyzed by logistic regression analysis and expressed as odds ratios (ORs) with 95% confidence intervals (CIs). Results: The median values of circulating leptin and adiponectin were 7.2 ng/mL (IQR 3.8-13.4) and 9.0 µg/mL (IQR 5.7-14.6), respectively. After adjustment for age, sex, body mass index, hypertension, diabetes, chronic obstructive pulmonary disease, and oxygen saturation at admission, a doubling of circulating adiponectin was associated with a 38% reduction in odds of 90-day mortality (OR 0.62, CI 0.43-0.89) and a 40% reduction in odds of respiratory failure (OR 0.60, CI 0.42-0.86). The association tended to be strongest in individuals below the median age of 72 years. Circulating leptin was not associated with outcomes. Conclusions: Circulating adiponectin at admission was inversely associated with mortality and respiratory failure in SARS-CoV-2 infection. Further studies are needed to elucidate how exactly adipokines, especially adiponectin, are linked to the progression and prognosis of COVID-19.

Treatment effect modifiers in hospitalised patients with COVID-19 receiving remdesivir and dexamethasone.

BACKGROUND: The combined effectiveness of remdesivir and dexamethasone in subgroups of hospitalised patients with COVID-19 is poorly investigated. METHODS: In this nationwide retrospective cohort study, we included 3826 patients with COVID-19 hospitalised between February 2020 and April 2021. The primary outcomes were use of invasive mechanical ventilation and 30-day mortality, comparing a cohort treated with remdesivir and dexamethasone with a previous cohort treated without remdesivir and dexamethasone. We used inverse probability of treatment weighting logistic regression to assess associations with progression to invasive mechanical ventilation and 30-day mortality between the two cohorts. The analyses were conducted overall and by subgroups based on patient characteristics. RESULTS: Odds ratio for progression to invasive mechanical ventilation and 30-day mortality in individuals treated with remdesivir and dexamethasone compared to treatment with standard of care alone was 0.46 (95% confidence interval, 0.37-0.57) and 0.47 (95% confidence interval, 0.39-0.56), respectively. The reduced risk of mortality was observed in elderly patients, overweight patients and in patients requiring supplemental oxygen at admission, regardless of sex, comorbidities and symptom duration. CONCLUSIONS: Patients treated with remdesivir and dexamethasone had significantly improved outcomes compared to patients treated with standard of care alone. These effects were observed in most patient subgroups.

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).

Myocardial Work in Patients Hospitalized With COVID-19: Relation to Biomarkers, COVID-19 Severity, and All-Cause Mortality.

Background COVID-19 infection has been hypothesized to affect left ventricular function; however, the underlying mechanisms and the association to clinical outcome are not understood. The global work index (GWI) is a novel echocardiographic measure of systolic function that may offer insights on cardiac dysfunction in COVID-19. We hypothesized that GWI was associated with disease severity and all-cause death in patients with COVID-19. Methods and Results In a multicenter study of patients admitted with COVID-19 (n=305), 249 underwent pressure-strain loop analyses to quantify GWI at a median time of 4 days after admission. We examined the association of GWI to cardiac biomarkers (troponin and NT-proBNP [N-terminal pro-B-type natriuretic peptide]), disease severity (oxygen requirement and CRP [C-reactive protein]), and all-cause death. Patients with elevated troponin (n=71) exhibited significantly reduced GWI (1508 versus 1707 mm Hg%; P=0.018). A curvilinear association to NT-proBNP was observed, with increasing NT-proBNP once GWI decreased below 1446 mm Hg%. Moreover, GWI was significantly associated with a higher oxygen requirement (relative increase of 6% per 100-mm Hg% decrease). No association was observed with CRP. Of the 249 patients, 37 died during follow-up (median, 58 days). In multivariable Cox regression, GWI was associated with all-cause death (hazard ratio, 1.08 [95% CI, 1.01-1.15], per 100-mm Hg% decrease), but did not increase C-statistics when added to clinical parameters. Conclusions In patients admitted with COVID-19, our findings indicate that NT-proBNP and troponin may be associated with lower GWI, whereas CRP is not. GWI was independently associated with all-cause death, but did not provide prognostic information beyond readily available clinical parameters. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04377035.

Early stimulated immune responses predict clinical disease severity in hospitalized COVID-19 patients.

Background: The immune pathogenesis underlying the diverse clinical course of COVID-19 is poorly understood. Currently, there is an unmet need in daily clinical practice for early biomarkers and improved risk stratification tools to help identify and monitor COVID-19 patients at risk of severe disease. Methods: We performed longitudinal assessment of stimulated immune responses in 30 patients hospitalized with COVID-19. We used the TruCulture whole-blood ligand-stimulation assay applying standardized stimuli to activate distinct immune pathways, allowing quantification of cytokine responses. We further characterized immune cell subsets by flow cytometry and used this deep immunophenotyping data to map the course of clinical disease within and between patients. Results: Here we demonstrate impairments in innate immune response pathways at time of COVID-19 hospitalization that are associated with the development of severe disease. We show that these impairments are transient in those discharged from hospital, as illustrated by functional and cellular immune reconstitution. Specifically, we identify lower levels of LPS-stimulated IL-1ß, and R848-stimulated IL-12 and IL-17A, at hospital admission to be significantly associated with increasing COVID-19 disease severity during hospitalization. Furthermore, we propose a stimulated immune response signature for predicting risk of developing severe or critical COVID-19 disease at time of hospitalization, to validate in larger cohorts. Conclusions: We identify early impairments in innate immune responses that are associated with subsequent COVID-19 disease severity. Our findings provide basis for early identification of patients at risk of severe disease which may have significant implications for the early management of patients hospitalized with COVID-19.

Behavioral factors associated with SARS-CoV-2 infection.

OBJECTIVE: To study the association between behavioural factors and incidence rates of SARS-CoV-2 infection. DESIGN: Case-control web-based questionnaire study. SETTING: Questionnaire data were collected in the Capital Region of Denmark in December 2020 when limited restrictions were in place, while the number of daily SARS-CoV-2 cases increased rapidly. PARTICIPANTS: 8913 cases of laboratory-confirmed SARS-CoV-2 infection were compared with two groups of controls: (1) 34 063 individuals with a negative SARS-CoV-2 test from the same date (negative controls, NCs) and 2) 25 989 individuals who had never been tested for a SARS-CoV-2 infection (untested controls, UC). Controls were matched on sex, age, test date and municipality. EXPOSURE: Activities during the 14 days prior to being tested positive for SARS-CoV-2 or during the same period for matched controls and precautions taken during the entire pandemic. MAIN OUTCOMES AND MEASURES: SARS-CoV-2 infection incidence rate ratios (IRR). RESULTS: Response rate was 41.4% (n=93 121). Using public transportation, grocery shopping (IRR: NC: 0.52; UC: 0.63) and outdoor sports activities (NC: 0.75; UC: 0.96) were not associated with increased rate of SARS-CoV-2 infection. Most precautions, for example, using hand sanitizer (NC: 0.79; UC: 0.98), physical distancing (NC: 0.79; UC: 0.82) and avoiding handshakes (NC: 0.74; UC: 0.77), were associated with a lower rate of infection. Activities associated with many close contacts, especially indoors, increased rate of infection. Except for working from home, all types of occupation were linked to increased rate of infection. CONCLUSIONS: In a community setting with moderate restrictions, activities such as using public transportation and grocery shopping with the relevant precautions were not associated with an increased rate of SARS-CoV-2 infection. Exposures and activities where safety measures are difficult to maintain might be important risk factors for infection. These findings may help public health authorities tailor their strategies for limiting the spread of SARS-CoV-2.

Antibody responses and risk factors associated with impaired immunological outcomes following two doses of BNT162b2 COVID-19 vaccination in patients with chronic pulmonary diseases.

INTRODUCTION: Responses to COVID-19 vaccination in patients with chronic pulmonary diseases are poorly characterised. We aimed to describe humoral responses following two doses of BNT162b2 mRNA COVID-19 vaccine and identify risk factors for impaired responses. METHODS: Prospective cohort study including adults with chronic pulmonary diseases and healthcare personnel as controls (1:1). Blood was sampled at inclusion, 3 weeks, 2 and 6 months after first vaccination. We reported antibody concentrations as geometric means with 95% CI of receptor binding domain (RBD)-IgG and neutralising antibody index of inhibition of ACE-2/RBD interaction (%). A low responder was defined as neutralising index in the lowest quartile (primary outcome) or RBD-IgG <225 AU/mL plus neutralising index <25% (secondary outcome), measured at 2 months. We tested associations using Poisson regression. RESULTS: We included 593 patients and 593 controls, 75% of all had neutralising index ≥97% at 2 months. For the primary outcome, 34.7% of patients (n=157/453) and 12.9% of controls (n=46/359) were low responders (p<0.0001). For the secondary outcome, 8.6% of patients (n=39/453) and 1.4% of controls (n=5/359) were low responders (p<0.001). Risk factors associated with low responder included increasing age (per decade, adjusted risk ratio (aRR) 1.17, 95% CI 1.03 to 1.32), Charlson Comorbidity Index (per point) (aRR 1.15, 95% CI 1.05 to 1.26), use of prednisolone (aRR 2.08, 95% CI 1.55 to 2.77) and other immunosuppressives (aRR 2.21, 95% CI 1.65 to 2.97). DISCUSSION: Patients with chronic pulmonary diseases established functional humoral responses to vaccination, however lower than controls. Age, comorbidities and immunosuppression were associated with poor immunological responses.

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.

Behavioral factors associated with SARS-CoV-2 infection

Objective To study the association between behavioural factors and incidence rates of SARS-CoV-2 infection. Design Case–control web-based questionnaire study. Setting Questionnaire data were collected in the Capital Region of Denmark in December 2020 when limited restrictions were in place, while the number of daily SARS-CoV-2 cases increased rapidly. Participants 8913 cases of laboratory-confirmed SARS-CoV-2 infection were compared with two groups of controls: (1) 34 063 individuals with a negative SARS-CoV-2 test from the same date (negative controls, NCs) and 2) 25 989 individuals who had never been tested for a SARS-CoV-2 infection (untested controls, UC). Controls were matched on sex, age, test date and municipality. Exposure Activities during the 14 days prior to being tested positive for SARS-CoV-2 or during the same period for matched controls and precautions taken during the entire pandemic. Main outcomes and measures SARS-CoV-2 infection incidence rate ratios (IRR). Results Response rate was 41.4% (n=93 121). Using public transportation, grocery shopping (IRR: NC: 0.52;UC: 0.63) and outdoor sports activities (NC: 0.75;UC: 0.96) were not associated with increased rate of SARS-CoV-2 infection. Most precautions, for example, using hand sanitizer (NC: 0.79;UC: 0.98), physical distancing (NC: 0.79;UC: 0.82) and avoiding handshakes (NC: 0.74;UC: 0.77), were associated with a lower rate of infection. Activities associated with many close contacts, especially indoors, increased rate of infection. Except for working from home, all types of occupation were linked to increased rate of infection. Conclusions In a community setting with moderate restrictions, activities such as using public transportation and grocery shopping with the relevant precautions were not associated with an increased rate of SARS-CoV-2 infection. Exposures and activities where safety measures are difficult to maintain might be important risk factors for infection. These findings may help public health authorities tailor their strategies for limiting the spread of SARS-CoV-2.

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).

Improved Survival Among Hospitalized Patients With Coronavirus Disease 2019 (COVID-19) Treated With Remdesivir and Dexamethasone. A Nationwide Population-Based Cohort Study.

BACKGROUND: There are limited data on outcomes of moderate to severe coronavirus disease 2019 (COVID-19) among patients treated with remdesivir and dexamethasone in a real-world setting. We sought to compare the effectiveness of standard of care (SOC) alone versus SOC plus remdesivir and dexamethasone. METHODS: Two population-based nationwide cohorts of individuals hospitalized with COVID-19 during February through December 2020 were studied. Death within 30 days and need of mechanical ventilation (MV) were compared by inverse probability of treatment weighted (ITPW) logistic regression analysis and shown as odds ratio (OR) with 95% confidence interval (CI). RESULTS: The 30-days mortality rate of 1694 individuals treated with remdesivir and dexamethasone in addition to SOC was 12.6% compared to 19.7% for 1053 individuals receiving SOC alone. This corresponded to a weighted OR of 30-day mortality of 0.47 (95% CI: .38-.57) for patients treated with remdesivir and dexamethasone compared to patients receiving SOC alone. Similarly, progression to MV was reduced (OR 0.36; 95% CI: .29-.46). CONCLUSIONS: Treatment of moderate to severe COVID-19 during June through December that included remdesivir and dexamethasone was associated with reduced 30-day mortality and need of MV compared to treatment in February through May.

Protective potential of high-intensity interval training on cardiac structure and function after COVID-19: protocol and statistical analysis plan for an investigator-blinded randomised controlled trial.

INTRODUCTION: COVID-19 is associated with a marked systemic inflammatory response with concomitant cardiac injury and remodelling, but it is currently unknown whether the latter is reversible. Given that high-intensity interval training (HIIT) is a powerful stimulus to improve cardiorespiratory fitness while also eliciting marked anti-inflammatory effects, it may be an important countermeasure of reducing cardiopulmonary morbidity following COVID-19. METHODS AND ANALYSIS: 40 COVID-19 survivors who have been discharged from hospital will be included in this investigator-blinded randomised study with a 12-week HIIT intervention. Patients will be 1:1 block-randomised by sex to either a supervised HIIT exercise group or standard care (control group). The main hypothesis is that a 12-week HIIT scheme is a safe way to improve loss of cardiac mass and associated cardiorespiratory fitness, despite hypothesised limited HIIT-induced changes in conventional lung function indices per se. Ultimately, we hypothesise that the HIIT scheme will reduce post-COVID-19 symptoms and improve quality of life. ETHICS AND DISSEMINATION: This study is approved by the Scientific Ethical Committee at the Capital Region of Denmark (H-20033733, including amendments 75068 and 75799) and registered at ClinicalTrials.gov (NCT04647734, pre-results). The findings will be published in a peer-reviewed journal, including cases of positive, negative and inconclusive results.Trial registration number NCT04549337.

Fidelity, tolerability and safety of acute high-intensity interval training after hospitalisation for COVID-19: a randomised cross-over trial.

OBJECTIVES: Many patients with COVID-19 suffer from persistent symptoms, many of which may potentially be reversed by high-intensity interval training (HIIT). Yet, the safety and tolerability of HIIT after COVID-19 is controversial. This study aimed to investigate the fidelity, tolerability and safety of three different HIIT protocols in individuals that had recently been hospitalised due to COVID-19. METHODS: The study was a randomised cross-over trial. We compared three supervised HIIT protocols (4×4, 6×1, 10-20-30) in 10 individuals recently discharged after hospitalisation for severe COVID-19. Each HIIT protocol had a duration of 38 min and was performed with a 1-week washout between them. Outcomes included adverse events, exercise training intensity and tolerability assessed by the Likert scale (1-10). RESULTS: All 10 participants aged 61 (mean, SD 8) years (5 males) completed all three HIIT protocols with no adverse events. High intensities were achieved in all three protocols, although they differed in terms of time spent with a heart rate ≥85% of maximum (mean (SD); 4×4: 13.7 (6.4) min; 10-20-30: 12.1 (3.8) min; 6×1: 6.1 (5.6) min; p=0.03). The three protocols were all well tolerated with similar Likert scale scores (mean (SD); 4×4: 8 (2), 10-20-30: 8 (2), 6×1: 9 (2), p=0.72). CONCLUSION: Our findings indicate that recently hospitalised individuals for severe COVID-19 may safely tolerate acute bouts of supervised HIIT as per protocol. This warrants future studies testing the potential of regular HIIT as a rehabilitation strategy in this context.

Lung ultrasound findings in hospitalized COVID-19 patients in relation to venous thromboembolic events: the ECHOVID-19 study.

PURPOSE: Several studies have reported thromboembolic events to be common in severe COVID-19 cases. We sought to investigate the relationship between lung ultrasound (LUS) findings in hospitalized COVID-19 patients and the development of venous thromboembolic events (VTE). METHODS: A total of 203 adults were included from a COVID-19 ward in this prospective multi-center study (mean age 68.6 years, 56.7% men). All patients underwent 8-zone LUS, and all ultrasound images were analyzed off-line blinded. Several LUS findings were investigated (total number of B-lines, B-line score, and LUS-scores). RESULTS: Median time from admission to LUS examination was 4 days (IQR: 2, 8). The median number of B-lines was 12 (IQR: 8, 18), and 44 (21.7%) had a positive B-line score. During hospitalization, 17 patients developed VTE (4 deep-vein thrombosis, 15 pulmonary embolism), 12 following and 5 prior to LUS. In fully adjusted multivariable Cox models (excluding participants with VTE prior to LUS), all LUS parameters were significantly associated with VTE (total number of B-lines: HR = 1.14, 95% CI (1.03, 1.26) per 1 B-line increase), positive B-line score: HR = 9.79, 95% CI (1.87, 51.35), and LUS-score: HR = 1.51, 95% CI (1.10, 2.07), per 1-point increase). The B-line score and LUS-score remained significantly associated with VTE in sensitivity analyses. CONCLUSION: In hospitalized COVID-19 patients, pathological LUS findings were common, and the total number of B-lines, B-line score, and LUS-score were all associated with VTE. These findings indicate that the LUS examination may be useful in risk stratification and the clinical management of COVID-19. These findings should be considered hypothesis generating. GOV ID: NCT04377035.

Remote continuous glucose monitoring during the COVID-19 pandemic in quarantined hospitalized patients in Denmark: A structured summary of a study protocol for a randomized controlled trial.

OBJECTIVES: Patients with diabetes are - compared to people without diabetes - at increased risk of worse outcomes from COVID-19 related pneumonia during hospitalization. We aim to investigate whether telemetric continuous glucose monitoring (CGM) in quarantined hospitalized patients with diabetes and confirmed SARS-CoV-2 infection or another contagious infection can be successfully implemented and is associated with better glycaemic control than usual blood glucose monitoring (finger prick method) and fewer patient-health care worker contacts. Furthermore, we will assess whether glucose variables are associated with the clinical outcome. The hypothesis is that by using remote CGM to monitor glucose levels of COVID-19 infected patients and patients with other contagious infections with diabetes, we can still provide satisfactory (and maybe even better) in-hospital diabetes management despite patients being quarantined. Furthermore, the number of patient-personnel contacts can be lowered compared to standard monitoring with finger-prick glucose. This could potentially reduce the risk of transmitting contagious diseases from the patient to other people and reduces the use of PPE's. Improved glucose control may reduce the increased risk of poor clinical outcomes associated with combined diabetes and infection. TRIAL DESIGN: This is a single centre, open label, exploratory, randomised, controlled, 2-arm parallel group (1:1 ratio), controlled trial. PARTICIPANTS: The trial population is patients with diabetes (both type 1 diabetes, type 2 diabetes, newly discovered diabetes that is not classified yet, and all other forms of diabetes) admitted to Nordsjællands Hospital that are quarantined due to COVID-19 infection or another infection. INCLUSION CRITERIA: 1. Hospitalized with confirmed COVID-19 infection by real-time PCR or another validated method OR hospitalized with a non-COVID-19 diagnosis and quarantined at time of inclusion. 2. A documented clinically relevant history of diabetes or newly discovered during hospitalization as defined by The World Health Organizations diagnostic criteria for diabetes. 3. Written informed consent obtained before any trial related procedures are performed. 4. Male or female aged over 18 years of age. 5. Must be able to communicate with the study personnel. 6. The subject must be willing and able to comply with trial protocol. EXCLUSION CRITERIA: 1. Known hypersensitivity to the band-aid of the Dexcom G6 sensors INTERVENTION AND COMPARATOR: Participants will be randomized to either real-time CGM with the Dexcom G6, a CGM system that does not need to be calibrated, or finger-prick glucose monitoring. Blinded CGM will be mounted in the finger-prick group. In the open CGM group, the glucose values will be transmitted to a Smartdevice in the nurse office where glucose levels can be monitored remotely. MAIN OUTCOMES: The primary endpoint is the difference between groups in distribution of glucose values being in time in range (TIR), defined as 3.9 to 10 mmol/l. In addition, the primary endpoint is reported as the percentage of days of the whole admission, the patient reaches TIR. Secondary endpoints are the estimated number of saved patient-personnel contacts related to blood glucose measurements, incl. time healthcare providers spent on diabetes related tasks and PPE related tasks, during the patients' hospitalization. Furthermore, we will assess additional glucose outcomes and associations of glucose variables and patient outcomes (As specified in the protocol). RANDOMISATION: The service used for generating the randomization lists is www.random.org . Randomization is stratified by COVID-19 status and an allocation ratio of 1:1 to either CGM or finger-prick groups. BLINDING (MASKING): The design of the trial is open, however blinded CGM is recorded in the finger-prick group. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): A sample size of N=72 is required for the primary endpoint analysis based on 80% power to detect a 10% difference between groups in TIR and to allow for a 15% dropout. The 72 participants will be randomized 1:1 to open CGM or finger-prick with 36 in each group. TRIAL STATUS: This structured protocol summary is based on the CGM-ISO protocol version 1.3, dated 13.05.2020. Date of first patient enrolled: 25.05.2020. Expected last recruiting is May 2021. Patients enrolled to date: 20 in total. 8 with confirmed COVID-19 infection and 12 with other infections. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04430608 . Registered 12.06.2020 FULL PROTOCOL: The full protocol is attached as an additional file from the Trial website (Additional file 1). In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; This Letter serves as a summary of the key elements of the full protocol.

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.

Characteristics and early outcomes of patients hospitalised for COVID-19 in North Zealand, Denmark

INTRODUCTION: Coronavirus disease 2019 (COVID-19) is an ongoing pandemic associated with significant morbidity and mortality worldwide. Limited data are available describing the clinical presentation and outcomes of hospitalised COVID-19 patients in Europe. METHODS: This was a single-centre retrospective chart review of all patients with COVID-19 admitted to the North Zealand Hospital in Denmark between 1 March and 4 May 2020. Main outcomes include major therapeutic interventions during hospitalisation, such as invasive mechanical ventilation, as well as death. RESULTS: A total of 115 patients were included, including four infants. The median age of adults was 68 years and 40% were female. At admission, 55 (50%) patients had a fever, 29 (26%) had a respiratory rate exceeding 24 breaths/minute, and 78 (70%) received supplemental oxygen. The prevalence of co-infection was 13%. Twenty patients (18%) (median age: 64 years;15% female) were treated in the intensive care unit. Twelve (10.4%) received invasive mechanical ventilation and three (2.6%) renal replacement therapy. Nine patients (8%) developed pulmonary embolism. Sixteen patients (14%) died. Among patients requiring mechanical ventilation (n = 12), seven (6.1%) were discharged alive, four (3.4%) died and one (0.9%) was still hospitalised. CONCLUSION: In this cohort of hospitalised COVID-19 patients, mortality was lower than in other Danish and European case series. FUNDING: none. TRIAL REGISTRATION: not relevant.