Effect of Single High Dose Vitamin D Substitution in Hospitalized COVID-19 Patients with Vitamin D Deficiency on Length of Hospital Stay.

Vitamin D and its role in the coronavirus-19 disease (COVID-19) pandemic has been controversially discussed, with inconclusive evidence about vitamin D3 (cholecalciferol) supplementation in COVID-19 patients. Vitamin D metabolites play an important role in the initiation of the immune response and can be an easily modifiable risk factor in 25-hydroxyvitamin D3 (25(OH)D3)-deficient patients. This is a multicenter, randomized, placebo-controlled double-blind trial to compare the effect of a single high dose of vitamin D3 followed by treatment as usual (TAU) of daily vitamin D3 daily until discharge versus placebo plus TAU in hospitalized patients with COVID-19 and 25(OH)D3-deficiency on length hospital stay. We included 40 patients per group and did not observe a significant difference in the median length of hospital stay (6 days in both groups, p = 0.920). We adjusted the length of stay for COVID-19 risk factors (ß = 0.44; 95% CI: -2.17-2.22), and center (ß = 0.74; 95% CI: -1.25-2.73). The subgroup analysis in patients with severe 25(OH)D3-deficiency (<25 nmol/L) showed a non-significant reduction in the median length of hospital stay in the intervention group (5.5 vs. 9 days, p = 0.299). The competing risk model with death did not reveal significant differences between the group in the length of stay (HR = 0.96, 95% CI 0.62-1.48, p = 0.850). Serum 25(OH)D3 level increased significantly in the intervention group (mean change in nmol/L; intervention: +26.35 vs. control: -2.73, p < 0.001). The intervention with 140,000 IU vitamin D3 + TAU did not significantly shorten the length of hospital stay but was effective and safe for the elevation of serum 25(OH)D3 levels.

Burden of disease in patients hospitalised with COVID-19 during the first and second pandemic wave in Switzerland: a nationwide cohort study.

AIM OF THE STUDY: The first and second waves of the COVID-19 pandemic led to a tremendous burden of disease and influenced several policy directives, prevention and treatment strategies as well as lifestyle and social behaviours. We aimed to describe trends of hospitalisations with COVID-19 and hospital-associated outcomes in these patients during the first two pandemic waves in Switzerland. METHODS: In this nationwide retrospective cohort study, we used in-hospital claims data of patients hospitalised with COVID-19 in Switzerland between January 1st and December 31st, 2020. First, stratified by wave (first wave: January to May, second wave: June to December), we estimated incidence rates (IR) and rate differences (RD) per 10,000 person-years of COVID-19-related hospitalisations across different age groups (0-9, 10-19, 20-49, 50-69, and ≥70 years). IR was calculated by counting the number of COVID-19 hospitalisations for each patient age stratum paired with the number of persons living in Switzerland during the specific wave period. Second, adjusted odds ratios (aOR) of outcomes among COVID-19 hospitalisations were calculated to assess the association between COVID-19 wave and outcomes, adjusted for potential confounders. RESULTS: Of 36,517 hospitalisations with COVID-19, 8,862 (24.3%) were identified during the first and 27,655 (75.7%) during the second wave. IR for hospitalisations with COVID-19 was highest during the second wave and among patients above 50 years (50-69 years: first wave: 31.49 per 10,000 person-years; second wave: 62.81 per 10,000 person-years; RD 31.32 [95% confidence interval [CI]: 29.56 to 33.08] per 10,000 person-years; IRR 1.99 [95% CI: 1.91 to 2.08]; ≥70 years: first wave: 88.59 per 10,000 person-years; second wave: 228.41 per 10,000 person-years; RD 139.83 [95% CI: 135.42 to 144.23] per 10,000 person-years; IRR 2.58 [95% CI: 2.49 to 2.67]). While there was no difference in hospital readmission, when compared with the first wave, patients hospitalised during the second wave had a lower probability of death (aOR 0.88 [95% CI: 0.81 to 0.95], ARDS (aOR 0.56 [95% CI: 0.51 to 0.61]), ICU admission (aOR 0.66 [95% CI: 0.61 to 0.70]), and need for ECMO (aOR 0.60 [95% CI: 0.38 to 0.92]). LOS was -16.1 % (95% CI: -17.8 to -14.2) shorter during the second wave. CONCLUSION: In this nationwide cohort study, rates of hospitalisations with COVID-19 were highest among adults older than 50 years and during the second wave. Except for hospital readmission, the likelihood of adverse outcomes was lower during the second pandemic wave, which may be explained by advances in the understanding of the disease and improved treatment options.

Identification of COVID-19 patients at risk of hospital admission and mortality: a European multicentre retrospective analysis of mid-regional pro-adrenomedullin.

BACKGROUND: Mid-Regional pro-Adrenomedullin (MR-proADM) is an inflammatory biomarker that improves the prognostic assessment of patients with sepsis, septic shock and organ failure. Previous studies of MR-proADM have primarily focussed on bacterial infections. A limited number of small and monocentric studies have examined MR-proADM as a prognostic factor in patients infected with SARS-CoV-2, however there is need for multicenter validation. An evaluation of its utility in predicting need for hospitalisation in viral infections was also performed. METHODS: An observational retrospective analysis of 1861 patients, with SARS-CoV-2 confirmed by RT-qPCR, from 10 hospitals across Europe was performed. Biomarkers, taken upon presentation to Emergency Departments (ED), clinical scores, patient demographics and outcomes were collected. Multiclass random forest classifier models were generated as well as calculation of area under the curve analysis. The primary endpoint was hospital admission with and without death. RESULTS: Patients suitable for safe discharge from Emergency Departments could be identified through an MR-proADM value of ≤ 1.02 nmol/L in combination with a CRP (C-Reactive Protein) of ≤ 20.2 mg/L and age ≤ 64, or in combination with a SOFA (Sequential Organ Failure Assessment) score < 2 if MR-proADM was ≤ 0.83 nmol/L regardless of age. Those at an increased risk of mortality could be identified upon presentation to secondary care with an MR-proADM value of > 0.85 nmol/L, in combination with a SOFA score ≥ 2 and LDH > 720 U/L, or in combination with a CRP > 29.26 mg/L and age ≤ 64, when MR-proADM was > 1.02 nmol/L. CONCLUSIONS: This international study suggests that for patients presenting to the ED with confirmed SARS-CoV-2 infection, MR-proADM in combination with age and CRP or with the patient's SOFA score could identify patients at low risk where outpatient treatment may be safe.

Association of Different Malnutrition Parameters and Clinical Outcomes among COVID-19 Patients: An Observational Study.

Background: Malnutrition is highly prevalent in medical inpatients and may also negatively influence clinical outcomes of patients hospitalized with COVID-19. We analyzed the prognostic implication of different malnutrition parameters with respect to adverse clinical outcomes in patients hospitalized with COVID-19. Methods: In this observational study, consecutively hospitalized adult patients with confirmed COVID-19 at the Cantonal Hospital Aarau (Switzerland) were included between February and December 2020. The association between Nutritional Risk Screening 2002 (NRS 2002) on admission, body mass index, and admission albumin levels with in-hospital mortality and secondary endpoints was studied by using multivariable regression analyses. Results: Our analysis included 305 patients (median age of 66 years, 66.6% male) with a median NRS 2002-score of 2.0 (IQR 1.0, 3.0) points. Overall, 44 patients (14.4%) died during hospitalization. A step-wise increase in mortality risk with a higher nutritional risk was observed. When compared to patients with no risk for malnutrition (NRS 2002 < 3 points), patients with a moderate (NRS 2002 3-4 points) or high risk for malnutrition (NRS 2002 ≥ 5 points) had a two-fold and five-fold increase in risk, respectively (10.5% vs. 22.7% vs. 50.0%, p < 0.001). The increased risk for mortality was also confirmed in a regression analysis adjusted for gender, age, and comorbidities (odds ratio for high risk for malnutrition 4.68, 95% CI 1.18 to 18.64, p = 0.029 compared to patients with no risk for malnutrition). Conclusions: In patients with COVID-19, the risk for malnutrition was a risk factor for in-hospital mortality. Future studies should investigate the role of nutritional treatment in this patient population.

Call, chosen, HA2T2, ANDC: validation of four severity scores in COVID-19 patients.

PURPOSE: To externally validate four previously developed severity scores (i.e., CALL, CHOSEN, HA2T2 and ANDC) in patients with COVID-19 hospitalised in a tertiary care centre in Switzerland. METHODS: This observational analysis included adult patients with a real-time reverse-transcription polymerase chain reaction or rapid-antigen test confirmed severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection hospitalised consecutively at the Cantonal Hospital Aarau from February to December 2020. The primary endpoint was all-cause in-hospital mortality. The secondary endpoint was disease progression, defined as needing invasive ventilation, ICU admission or death. RESULTS: From 399 patients (mean age 66.6 years ± 13.4 SD, 68% males), we had complete data for calculating the CALL, CHOSEN, HA2T2 and ANDC scores in 297, 380, 151 and 124 cases, respectively. Odds ratios for all four scores showed significant associations with mortality. The discriminative power of the HA2T2 score was higher compared to CALL, CHOSEN and ANDC scores [area under the curve (AUC) 0.78 vs. 0.65, 0.69 and 0.66, respectively]. Negative predictive values (NPV) for mortality were high, particularly for the CALL score (≥ 6 points: 100%, ≥ 9 points: 95%). For disease progression, discriminative power was lower, with the CHOSEN score showing the best performance (AUC 0.66). CONCLUSION: In this external validation study, the four analysed scores had a lower performance compared to the original cohorts regarding prediction of mortality and disease progression. However, all scores were significantly associated with mortality and the NPV of the CALL and CHOSEN scores in particular allowed reliable identification of patients at low risk, making them suitable for outpatient management.

Prevalence of Micronutrient Deficiencies in Patients Hospitalized with COVID-19: An Observational Cohort Study.

BACKGROUND: A higher risk for severe clinical courses of coronavirus disease 2019 (COVID-19) has been linked to deficiencies of several micronutrients. We therefore studied the prevalence of deficiencies of eight different micronutrients in a cohort of hospitalized COVID-19-patients. METHODS: We measured admission serum/plasma levels of vitamins A, B12, D, and E, as well as folic acid, zinc, selenium, and copper in 57 consecutively admitted adult patients with confirmed COVID-19 and analyzed prevalence of micronutrient deficiencies and correlations among micronutrient levels. Further, we studied associations of micronutrient levels with severe disease progression, a composite endpoint consisting of in-hospital mortality and/or need for intensive care unit (ICU) treatment with logistic regression. RESULTS: Median age was 67.0 years (IQR 60.0, 74.2) and 60% (n = 34) were male. Overall, 79% (n = 45) of patients had at least one deficient micronutrient level and 33% (n = 19) had ≥3 deficiencies. Most prevalent deficiencies were found for selenium, vitamin D, vitamin A, and zinc (51%, 40%, 39%, and 39%, respectively). We found several correlations among micronutrients with correlation coefficients ranging from r = 0.27 to r = 0.42. The strongest associations with lower risk for severe COVID-19 disease progression (adjusted odds ratios) were found for higher levels of vitamin A (0.18, 95% CI 0.05-0.69, p = 0.01), zinc (0.73, 95% CI 0.55-0.98, p = 0.03), and folic acid (0.88, 95% CI 0.78-0.98, p = 0.02). CONCLUSIONS: We found a high prevalence of micronutrient deficiencies in mostly older patients hospitalized for COVID-19, particularly regarding selenium, vitamin D, vitamin A, and zinc. Several deficiencies were associated with a higher risk for more severe COVID-19 courses. Whether supplementation of micronutrients is useful for prevention of severe clinical courses or treatment of COVID-19 warrants further research.

High-dose vitamin D substitution in patients with COVID-19: study protocol for a randomized, double-blind, placebo-controlled, multi-center study-VitCov Trial.

BACKGROUND: The coronavirus disease 19 (COVID-19) pandemic has caused millions of deaths, and new treatments are urgently needed. Factors associated with a worse COVID-19 prognosis include old age (> 65 years), ethnicity, male sex, obesity, and people with comorbidities. Furthermore, vitamin D deficiency was reported as a predictor of poor prognosis in patients with acute respiratory failure due to COVID-19. According to a recent clinical case series, vitamin D deficiency is a modifiable risk factor, which has the prospect of reducing hospital stay, intensive care, and fatal outcomes. Vitamin D has potent immunomodulatory properties, and its supplementation might improve important outcomes in critically ill and vitamin D-deficient COVID-19 patients. Despite the evidence that supports an association between vitamin D deficiency and COVID-19 severity, there is uncertainty about the direct link. Therefore, the aim of the trial is to assess if high-dose vitamin D supplementation has a therapeutic effect in vitamin D-deficient patients with COVID-19. METHODS: As the trial design, a randomized, placebo-controlled, double-blind, multi-center approach was chosen to compare a high single dose of vitamin D (140,000 IU) followed by treatment as usual (TAU) (VitD + TAU) with treatment as usual only (placebo + TAU) in patients with COVID-19 and vitamin D deficiency. DISCUSSION: Vitamin D substitution in patients with COVID-19 and vitamin D deficiency should be investigated for efficacy and safety. The study aim is to test the hypothesis that patients with vitamin D deficiency suffering from COVID-19 treated under standardized conditions in hospital will recover faster when additionally treated with high-dose vitamin D supplementation. Latest studies suggest that vitamin D supplementation in patients with COVID-19 is highly recommended to positively influence the course of the disease. With this randomized controlled trial, a contribution to new treatment guidelines shall be made. TRIAL REGISTRATION: ClinicalTrials.gov NCT04525820 and SNCTP 2020-01401.

Long COVID 1 year after hospitalisation for COVID-19: a prospective bicentric cohort study.

AIMS OF THE STUDY: There is increasing interest in better understanding of long COVID, a condition characterised by long-term sequelae ­ appearing or persisting after the typical convalescence period ­ of coronavirus disease 2019 (COVID-19). Herein, we describe long-term outcomes regarding residual symptoms and psychological distress in hospitalised patients 1 year after COVID-19. METHODS: This prospective cohort study included consecutive adult patients hospitalised for confirmed COVID-19 in two Swiss tertiary-care hospitals between March and June 2020. The primary endpoint was evidence of long COVID 1 year after discharge, defined as ≥1 persisting or new symptom related to COVID-19, from a predefined list of symptoms. Secondary endpoints included psychological distress and symptoms of post-traumatic stress disorder (PTSD). RESULTS: Among 90 patients included in the study, 63 (70%) had symptoms of long COVID 1 year after hospitalisation, particularly fatigue (46%), concentration difficulties (31%), shortness of breath (21%) and post-exertion malaise (20%). Three predictors, namely duration of hospitalisation (odds ratio [OR] 1.11, 95% confidence interval [CI] 1.00­1.22; p = 0.041), severity of illness (OR 1.19, 95% CI 1.04­1.37; p = 0.013), and self-perceived overall health status 30 days after hospitalisation (OR 0.97, 95% CI 0.94­1.00; p = 0.027) were associated with long COVID. Regarding secondary endpoints, 16 (18%) experienced psychological distress and 3 (3.3%) patients had symptoms of PTSD. CONCLUSION: A high proportion of COVID-19 patients report symptoms of long COVID 1 year after hospitalisation, which negatively affects their quality of life. The most important risk factors were severe initial presentation of COVID-19 with long hospital stays.

Procalcitonin for individualizing antibiotic treatment: an update with a focus on COVID-19.

Procalcitonin (PCT) is useful for differentiating between viral and bacterial infections and for reducing the unnecessary use of antibiotics. As the rise of antimicrobial resistance reaches "alarming" levels according to the World Health Organization, the importance of using biomarkers, such as PCT to limit unnecessary antibiotic exposure has further increased. Randomized trials in patients with respiratory tract infections have shown that PCT has prognostic implications and its use, embedded in stewardship protocols, leads to reductions in the use of antibiotics in different clinical settings without compromising clinical outcomes. However, available data are heterogeneous and recent trials found no significant benefit. Still, from these trials, we have learned several key considerations for the optimal use of PCT, which depend on the clinical setting, severity of presentation, and pretest probability for bacterial infection. For patients with respiratory infections and sepsis, PCT can be used to determine whether to initiate antimicrobial therapy in low-risk settings and, together with clinical data, whether to discontinue antimicrobial therapy in certain high-risk settings. There is also increasing evidence regarding PCT-guided therapy in patients with coronavirus disease 2019 (COVID-19). This review provides an up-to-date overview of the use of PCT in different clinical settings and diseases, including a discussion about its potential to improve the care of patients with COVID-19.

Comparison of characteristics, predictors and outcomes between the first and second COVID-19 waves in a tertiary care centre in Switzerland: an observational analysis.

AIM OF THE STUDY: To compare admission characteristics, predictors and outcomes of patients with confirmed coronavirus disease 2019 (COVID-19) hospitalised in a tertiary care hospital in Switzerland during the first and second waves of the pandemic. METHODS: This retrospective observational analysis included adult patients with  severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection confirmed by a real-time reverse transcriptase polymerase chain reaction (RT-PCR) or rapid antigen test and hospitalised at the Cantonal Hospital Aarau from 26 February to 30 April 2020 (first wave) and from 1 October to 31 December 2020 (second wave). The primary endpoint was all-cause in-hospital mortality. The secondary endpoints were transfer to the intensive care unit (ICU) and length of hospital stay (LOS). RESULTS: Overall, 486 patients (mean age 65.9 years ± 14.7 SD, 65% male) were included. Ninety-two patients (19%) died during the hospital stay and 92 patients (19%) were transferred to the ICU. Admission characteristics, including comorbidities and frailty, were similar for patients of the first (n = 100) and second wave (n = 386). However, during the second wave the median time from symptom onset to presentation to the emergency department (ED) was shorter (7 days, interquartile range [IQR] 4–9 vs 8 days, IQR 4–11; p = 0.02). In the second wave, most patients received high-dose glucocorticoid treatment (0% vs 76%, p <0.01). In-hospital mortality was similar among COVID-19 patients in the first (19/100, 19%) and second wave (73/386, 19%); this finding persisted after full adjustment in multiple regression models (adjusted odds ratio [aOR] 1.18, 95% confidence interval [CI] 0.49–2.80; p = 0.71). Risk for ICU admission was also similar (24% vs 18%; aOR 0.98, 95% CI 0.46–2.06; p = 0.95). More patients were transferred to rehabilitation facilities in the second wave (18% vs 31%; aOR 2.06, 95% CI 1.04–4.07; p = 0.04) and LOS was 2.5 days shorter (9.0 vs 6.5 days; adjusted difference −2.53 days, 95%-CI −4.51 to −0.54; p = 0.01). Main predictors for in-hospital death were patient age (aOR 1.07, 95% CI 1.02–1.11; p <0.01), male sex (aOR 2.41, 95% CI 1.05–5.55; p = 0.04) and the age-adjusted Charlson comorbidity index (aOR 1.27, 95% CI 1.09–1.48 p <0.01). CONCLUSION: Despite differing treatment regimens, mortality and ICU admission remained largely unchanged for COVID-19 patients admitted during the second wave of the pandemic in our tertiary care hospital. However, discharge processes were optimised with patients leaving the hospital earlier and going to rehabilitation facilities more often.  .

Activation of Vasopressin System During COVID-19 is Associated With Adverse Clinical Outcomes: An Observational Study.

BACKGROUND: Activation of the vasopressin system plays a key role for the maintenance of osmotic, cardiovascular, and stress hormone homeostasis during disease. We investigated levels of copeptin, the C-terminal segment of the vasopressin prohormone, that mirrors the production rate of vasopressin in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We measured levels of copeptin on admission and after days 3/4, 5/6, and 7/8 in 74 consecutive hospitalized adult COVID-19 patients and compared its prognostic accuracy to that of patients with community-acquired pneumonia (n = 876) and acute or chronic bronchitis (n = 371) from a previous study by means of logistic regression analysis. The primary endpoint was all-cause 30-day mortality. RESULTS: Median admission copeptin levels in COVID-19 patients were almost 4-fold higher in nonsurvivors compared with survivors (49.4 pmol/L [iterquartile range (IQR) 24.9-68.9 pmol/L] vs 13.5 pmol/L [IQR 7.0-26.7 pmol/L]), resulting in an age- and gender-adjusted odds ratio of 7.0 (95% confidence interval [CI] 1.2-40.3), p < 0.03 for mortality. Higher copeptin levels in nonsurvivors persisted during the short-term follow-up. Compared with the control group patients with acute/chronic bronchitis and pneumonia, COVID-19 patients did not have higher admission copeptin levels. CONCLUSIONS: A pronounced activation of the vasopressin system in COVID-19 patients is associated with an adverse clinical course in COVID-19 patients. This finding, however, is not unique to COVID-19 but similar to other types of respiratory infections.

Influence of Prednisone on Inflammatory Biomarkers in Community-Acquired Pneumonia: Secondary Analysis of a Randomized Trial.

Glucocorticoids are frequently prescribed in inflammatory diseases and have recently experienced a boom in the treatment of COVID-19. Small studies have shown an effect of glucocorticoids on inflammatory marker levels, but definitive proof is lacking. We investigated the influence of prednisone on inflammatory biomarkers in a previous multicenter, randomized, placebo-controlled trial that compared a 7-day treatment course of 50-mg prednisone to placebo in patients hospitalized with community-acquired pneumonia. We compared levels of C-reactive protein (CRP), procalcitonin (PCT), leukocyte and neutrophil count between patients with and without glucocorticoid treatment at baseline and on days 3, 5, and 7 and at discharge by Wilcoxon tests and analysis of variance. A total of 356 patient data sets in the prednisone group and 355 in the placebo group were available for analysis. Compared to placebo, use of prednisone was associated with reductions in levels of CRP on days 3, 5, and 7 (mean difference of 46%, P < .001 for each time point). For PCT, no such difference was observed. Leukocyte and neutrophil count were higher in the prednisone group at all time points (mean difference of 27% for leukocytes and 33% for neutrophils, P <.001 for all time points). We conclude that after administration of glucocorticoids in community-acquired pneumonia, patients had lower CRP levels and increased leukocyte and neutrophil count as compared to the placebo group. PCT levels were not different between treatment groups. PCT levels thus may more appropriately mirror the resolution of infection compared to more traditional inflammatory markers.

Psychological burden in patients with COVID-19 and their relatives 90 days after hospitalization: A prospective observational cohort study.

OBJECTIVE: COVID-19 causes psychological distress for patients and their relatives at short term. However, little research addressed the longer-term psychological outcomes in this population. Therefore, we aimed to prospectively assess clinically relevant psychological distress in hospitalized patients with COVID-19 and their relatives 90 days after hospital discharge. METHODS: This exploratory, prospective, observational cohort study included consecutive adult patients hospitalized in two Swiss tertiary-care hospitals between March and June 2020 for confirmed COVID-19 and their relatives. The primary outcome was psychological distress defined as clinically relevant symptoms of anxiety and/or depression measured with the Hospital Anxiety and Depression Scale (HADS) 90 days after discharge. RESULTS: Clinically relevant psychological distress 90 days after hospital discharge was present in 23/108 patients (21.3%) and 22/120 relatives (18.3%). For patients, risk and protective factors associated with clinically relevant psychological distress included sociodemographic, illness-related, psychosocial, and hospital-related factors. A model including these factors showed good discrimination, with an area under the receiver-operating characteristic curve (AUC) of 0.84. For relatives, relevant risk factors were illness-related, psychosocial, and hospital-related factors. Resilience was negatively associated with anxiety and depression in both patients and relatives and regarding PTSD in relatives only. CONCLUSION: COVID-19 is linked to clinically relevant psychological distress in a subgroup of patients and their relatives 90 days after hospitalization. If confirmed in an independent and larger patient cohort, knowledge about these potential risk and protective factors might help to develop preventive strategies.

Association of endothelial activation assessed through endothelin-I precursor peptide measurement with mortality in COVID-19 patients: an observational analysis.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) has been linked to thrombotic complications and endothelial dysfunction. We assessed the prognostic implications of endothelial activation through measurement of endothelin-I precursor peptide (proET-1), the stable precursor protein of Endothelin-1, in a well-defined cohort of patients hospitalized with COVID-19. METHODS: We measured proET-1 in 74 consecutively admitted adult patients with confirmed COVID-19 and compared its prognostic accuracy to that of patients with community-acquired pneumonia (n = 876) and viral bronchitis (n = 371) from a previous study by means of logistic regression analysis. The primary endpoint was all-cause 30-day mortality. RESULTS: Overall, median admission proET-1 levels were lower in COVID-19 patients compared to those with pneumonia and exacerbated bronchitis, respectively (57.0 pmol/l vs. 113.0 pmol/l vs. 96.0 pmol/l, p < 0.01). Although COVID-19 non-survivors had 1.5-fold higher admission proET-1 levels compared to survivors (81.8 pmol/l [IQR: 76 to 118] vs. 53.6 [IQR: 37 to 69]), no significant association of proET-1 levels and mortality was found in a regression model adjusted for age, gender, creatinine level, diastolic blood pressure as well as cancer and coronary artery disease (adjusted OR 0.1, 95% CI 0.0009 to 14.7). In patients with pneumonia (adjusted OR 25.4, 95% CI 5.1 to 127.4) and exacerbated bronchitis (adjusted OR 120.1, 95% CI 1.9 to 7499) we found significant associations of proET-1 and mortality. CONCLUSIONS: Compared to other types of pulmonary infection, COVID-19 shows only a mild activation of the endothelium as assessed through measurement of proET-1. Therefore, the high mortality associated with COVID-19 may not be attributed to endothelial dysfunction by the surrogate marker proET-1.

Prevalence and factors associated with psychological burden in COVID-19 patients and their relatives: A prospective observational cohort study.

BACKGROUND: Due to the dramatic measures accompanying isolation and the general uncertainty and fear associated with COVID-19, patients and relatives may be at high risk for adverse psychological outcomes. Until now there has been limited research focusing on the prevalence of psychological distress and associated factors in COVID-19 patients and their relatives. The objective of our study was to assess psychological distress in COVID-19 patients and their relatives 30 days after hospital discharge. METHODS: In this prospective observational cohort study at two Swiss tertiary-care hospitals we included consecutive adult patients hospitalized between March and June 2020 for a proven COVID-19 and their relatives. Psychological distress was defined as symptoms of anxiety and/or depression measured with the Hospital Anxiety and Depression Scale (HADS), i.e., a score of ≥8 on the depression and/or anxiety subscale. We further evaluated symptoms of post-traumatic stress disorder (PTSD), defined as a score of ≥1.5 on the Impact of Event Scale-Revised (IES-R). RESULTS: Among 126 included patients, 24 (19.1%) had psychological distress and 10 (8.7%) had symptoms of PTSD 30 days after hospital discharge. In multivariate logistic regression analyses three factors were independently associated with psychological distress in patients: resilience (OR 0.82; 95%CI 0.71 to 0.94; p = 0.005), high levels of perceived stress (OR 1.21; 95%CI 1.06 to 1.38; p = 0.006) and low frequency of contact with relatives (OR 7.67; 95%CI 1.42 to 41.58; p = 0.018). The model showed good discrimination, with an area under the receiver-operating characteristic curve (AUC) of 0.92. Among 153 relatives, 35 (22.9%) showed symptoms of psychological distress, and 3 (2%) of PTSD. For relatives, resilience was negatively associated (OR 0.85; 95%CI 0.75 to 0.96; p = 0.007), whereas perceived overall burden caused by COVID-19 was positively associated with psychological distress (OR 1.72; 95%CI 1.31 to 2.25; p<0.001). The overall model also had good discrimination, with an AUC of 0.87. CONCLUSION: A relevant number of COVID-19 patients as well as their relatives exhibited psychological distress 30 days after hospital discharge. These results might aid in development of strategies to prevent psychological distress in COVID-19 patients and their relatives.

How are rapid diagnostic tests for infectious diseases used in clinical practice: a global survey by the International Society of Antimicrobial Chemotherapy (ISAC).

Novel rapid diagnostic tests (RDTs) offer huge potential to optimise clinical care and improve patient outcomes. In this study, we aim to assess the current patterns of use around the world, identify issues for successful implementation and suggest best practice advice on how to introduce new tests. An electronic survey was devised by the International Society of Antimicrobial Chemotherapy (ISAC) Rapid Diagnostics and Biomarkers working group focussing on the availability, structure and impact of RDTs around the world. It was circulated to ISAC members in December 2019. Results were collated according to the UN human development index (HDI). 81 responses were gathered from 31 different countries. 84% of institutions reported the availability of any test 24/7. In more developed countries, this was more for respiratory viruses, whereas in high and medium/low developed countries, it was for HIV and viral hepatitis. Only 37% of those carrying out rapid tests measured the impact. There is no 'one-size fits all' solution to RDTs: the requirements must be tailored to the healthcare setting in which they are deployed and there are many factors that should be considered prior to this.

Renin-angiotensin-aldosterone system peptide profiles in patients with COVID-19.

OBJECTIVE: While evidence on the interface between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the renin-angiotensin-aldosterone-system (RAAS) is accumulating, clinical data on RAAS peptide alteration among coronavirus disease-19 (COVID-19) patients is missing. DESIGN AND METHODS: In this exploratory study, we prospectively included adult patients (aged ≥ 18 years) admitted between February 26 and April 30, 2020 to a tertiary care hospital in Switzerland. We assessed the association of an underlying SARS-CoV-2 infection and equilibrium serum levels of RAAS peptides in hospitalized COVID-19 patients 1:1 propensity-score matched with patients suffering from SARS-CoV-2-negative respiratory infections. Subgroup analyses involved stratification for taking RAAS inhibitors. RESULTS: COVID-19 patients had about 50% lower equilibrium serum RAAS peptide levels as compared with matched controls (angiotensin I: 31.6 vs 66.8 pmol/L, -52.7% (95%CI: -68.5% to -36.9%); angiotensin II: 37.7 vs 92.5 pmol/L, -59.2% (95%CI: -72.1% to -46.3%); angiotensin (1-5): 3.3 vs 6.6 pmol/L, -49.7% (95%CI: -59.2% to -40.2%); angiotensin (1-7): 4.8 vs 7.6 pmol/L, -64.9% (95%CI: -84.5% to -45.3%)). While the plasma renin activity was lower in COVID-19 patients (88.6 vs 207.9 pmol/L, -58.5% (95%CI: -71.4% to -45.6%)), there was no difference of angiotensin-converting enzyme (ACE) and ACE2 plasma activity between the groups. Subgroup analyses revealed a pronounced RAAS peptide profile depression in COVID-19 patients among those not on RAAS inhibitors. CONCLUSIONS: As compared with SARS-CoV-2-negative patients, we found a downregulated RAAS in presence of a SARS-CoV-2 infection. Whether the lower levels of the protective angiotensin (1-5) and (1-7) are linked to adverse outcomes in COVID-19 warrants further investigation.

The vasoactive peptide MR-pro-adrenomedullin in COVID-19 patients: an observational study.

OBJECTIVES: Midregional pro-adrenomedullin (MR-proADM) is a vasoactive peptide with key roles in reducing vascular hyperpermeability and thereby improving endothelial stability during infection. While MR-proADM is useful for risk stratification in patients with sepsis, clinical data about prediction accuracy in patients with severe acute respiratory syndrome coronavirus 2 disease (COVID-19) is currently missing. METHODS: We included consecutively adult patients hospitalized for confirmed COVID-19 at a tertiary care center in Switzerland between February and April 2020. We investigated the association of MR-proADM levels with in-hospital mortality in logistic regression and discrimination analyses. RESULTS: Of 89 included COVID-19 patients, 19% (n=17) died while in the hospital. Median admission MR-proADM levels (nmol/L) were increased almost 1.5-fold increased in non-survivors compared to survivors (1.3 [interquartile range IQR 1.1-2.3]) vs. 0.8 [IQR 0.7-1.1]) and showed good discrimination (area under the curve 0.78). An increase of 1 nmol/L of admission MR-proADM was independently associated with a more than fivefold increase in in-hospital mortality (adjusted odds ratio of 5.5, 95% confidence interval 1.4-21.4, p=0.015). An admission MR-proADM threshold of 0.93 nmol/L showed the best prognostic accuracy for in-hospital mortality with a sensitivity of 93%, a specificity of 60% and a negative predictive value of 97%. Kinetics of follow-up MR-proADM provided further prognostic information for in-hospital treatment. CONCLUSIONS: Increased levels of MR-proADM on admission and during hospital stay were independently associated with in-hospital mortality and may allow a better risk stratification, and particularly rule-out of fatal outcome, in COVID-19 patients.

Effect of nutritional support in patients with lower respiratory tract infection: Secondary analysis of a randomized clinical trial.

BACKGROUND: In polymorbid patients with bronchopulmonary infection, malnutrition is an independent risk factor for mortality. There is a lack of interventional data investigating whether providing nutritional support during the hospital stay in patients at risk for malnutrition presenting with lower respiratory tract infection lowers mortality. METHODS: For this secondary analysis of a randomized clinical trial (EFFORT), we analyzed data of a subgroup of patients with confirmed lower respiratory tract infection from an initial cohort of 2028 patients. Patients at nutritional risk (Nutritional Risk Screening [NRS] score ≥3 points) were randomized to receive protocol-guided individualized nutritional support to reach protein and energy goals (intervention group) or standard hospital food (control group). The primary endpoint of this analysis was all-cause 30-day mortality. RESULTS: We included 378 of 2028 EFFORT patients (mean age 74.4 years, 24% with COPD) into this analysis. Compared to usual care hospital nutrition, individualized nutritional support to reach caloric and protein goals showed a similar beneficial effect of on the risk of mortality in the subgroup of respiratory tract infection patients as compared to the main EFFORT trial (odds ratio 0.47 [95%CI 0.17 to 1.27, p = 0.136] vs 0.65 [95%CI 0.47 to 0.91, p = 0.011]) with no evidence of a subgroup effect (p for interaction 0.859). Effects were also similar among different subgroups based on etiology and type of respiratory tract infection and for other secondary endpoints. CONCLUSION: This subgroup analysis from a large nutrition support trial suggests that patients at nutritional risk as assessed by NRS 2002 presenting with bronchopulmonary infection to the hospital likely have a mortality benefit from individualized inhospital nutritional support. The small sample size and limited statistical power calls for larger nutritional studies focusing on this highly vulnerable patient population. CLINICAL TRIAL REGISTRATION: Registered under ClinicalTrials.gov Identifier no. NCT02517476.