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.

Antibiotic treatment durations for common infectious diseases in Switzerland: comparison between real-life and local and international guideline recommendations.

OBJECTIVES: Shortening the duration of antibiotic therapy (DAT) for common infectious diseases may be an effective strategy to tackle antimicrobial resistance. Shorter DAT has been proven safe and effective for community-acquired pneumonia (CAP), cellulitis, and cholangitis. METHODS: In a retrospective multicentre quality-control study, medical records of 770 patients hospitalized with CAP, cellulitis, and cholangitis at three tertiary care hospitals in Switzerland during 2017-2018 were randomly selected. Appropriateness of antibiotic treatment duration was assessed according to international and local guidelines. RESULTS: Records of 271, 260, and 239 patients with CAP, cellulitis, and cholangitis were included, respectively. Median DAT was seven days (interquartile range [IQR] 6-9), ten days (IQR 8-13), and nine days (IQR 6-13) in CAP, cellulitis, and cholangitis, respectively. DAT longer than recommended by local and international guidelines was observed in 32% and 37% of CAP patients, 23% and 70% of cellulitis patients, and 33% and 37% of cholangitis patients, respectively. Positive blood cultures (odds ratio [OR] = 2.42 (95% confidence interval [CI] 1.33-4.34]), infectious diseases consultation (OR = 1.79 [95% CI 1.05-2.78]), impaired renal function (OR = 0.99 [95% CI 0.98-1.00] per 1 ml/min / 1.73 m2 increase in estimated glomerular filtration rate) and a higher degree of inflammation on admission (OR = 1.0 [95% CI 1.001-1.005] per 10 mg/L increase in C-reactive protein) were independently associated with a DAT longer than recommended in international guidelines. CONCLUSIONS: DAT exceeded recommendations in a significant proportion of patients with mostly community-acquired infections.

Higher risk for influenza-associated pulmonary aspergillosis (IAPA) in asthmatic patients: A Swiss multicenter cohort study on IAPA in critically ill influenza patients.

BACKGROUND: Influenza-associated pulmonary aspergillosis (IAPA) is an important complication of severe influenza with high morbidity and mortality. METHODS: We conducted a retrospective multicenter study in tertiary hospitals in Switzerland during 2017/2018 and 2019/2020 influenza seasons. All adults with PCR-confirmed influenza infection and treatment on intensive-care unit (ICU) for >24 h were included. IAPA was diagnosed according to previously published clinical, radiological, and microbiological criteria. We assessed risk factors for IAPA and predictors for poor outcome, which was a composite of in-hospital mortality, ICU length of stay ≥7 days, mechanical ventilation ≥7 days, or extracorporeal membrane oxygenation. RESULTS: One hundred fifty-eight patients (median age 64 years, 45% females) with influenza were included, of which 17 (10.8%) had IAPA. Asthma was more common in IAPA patients (17% vs. 4% in non-IAPA, P = 0.05). Asthma (OR 12.0 [95% CI 2.1-67.2]) and days of mechanical ventilation (OR 1.1 [1.1-1.2]) were associated with IAPA. IAPA patients frequently required organ supportive therapies including mechanical ventilation (88% in IAPA vs. 53% in non-IAPA, P = 0.001) and vasoactive support (75% vs. 45%, P = 0.03) and had more complications including ARDS (53% vs. 26%, P = 0.04), respiratory bacterial infections (65% vs. 37%, P = 0.04), and higher ICU-mortality (35% vs. 16.4%, P = 0.05). IAPA (OR 28.8 [3.3-253.4]), influenza A (OR 3.3 [1.4-7.8]), and higher SAPS II score (OR 1.07 [1.05-1.10]) were independent predictors of poor outcome. INTERPRETATION: High clinical suspicion, early diagnostics, and therapy are indicated in IAPA because of high morbidity and mortality. Asthma is likely an underappreciated risk factor for IAPA.

Surgical Site Infections Associated With Implanted Pulse Generators for Deep Brain Stimulation: Meta-Analysis and Systematic Review.

OBJECTIVES: The aim of this study was to identify and systematically analyze relevant literature on surgical site infections (SSIs) associated with implantable pulse generator (IPG) procedures for deep brain stimulation (DBS). MATERIALS AND METHODS: In compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we conducted a systematic review and meta-analyses of 58 studies that reported SSI rates of 11,289 patients and 15,956 IPG procedures. A meta-analysis of proportions was performed to estimate the pooled proportion of SSIs across DBS procedures in general and to estimate the proportion of SSIs that occur at the IPG pocket. Moreover, a meta-analysis of odds ratio (OR) was conducted on those studies that reported their results of applying topical vancomycin powder during closure of the IPG wound. Results are presented as rates and OR with 95% CIs. RESULTS: The pooled proportion of SSIs was 4.9% (95% CI, 4.1%-6.1%) among all DBS procedures. The dominant SSI localization was the IPG pocket in 61.2% (95% CI, 53.4%-68.5%). A trend toward a beneficial effect of vancomycin powder over standard wound closure was found with an OR of 0.46 (95% CI, 0.21-1.02). Most studies (79.1%) that reported their treatment strategy in case of SSI had a strict protocol of removal of the IPG, followed by antimicrobial treatment and reimplantation of the IPG once the SSI had been eradicated. CONCLUSIONS: The IPG pocket was identified as the main site of SSI after DBS procedures. Most studies recommend complete IPG removal, antimicrobial treatment, and reimplantation of an IPG once the SSI has been eradicated. Future studies are needed to clarify the role of alternative approaches (eg, topical vancomycin powder) in the prevention of SSI associated with IPG.

Canakinumab in patients with COVID-19 and type 2 diabetes - A multicentre, randomised, double-blind, placebo-controlled trial.

Background: Patients with type 2 diabetes and obesity have chronic activation of the innate immune system possibly contributing to the higher risk of hyperinflammatory response to SARS-CoV2 and severe COVID-19 observed in this population. We tested whether interleukin-1ß (IL-1ß) blockade using canakinumab improves clinical outcome. Methods: CanCovDia was a multicenter, randomised, double-blind, placebo-controlled trial to assess the efficacy of canakinumab plus standard-of-care compared with placebo plus standard-of-care in patients with type 2 diabetes and a BMI > 25 kg/m2 hospitalised with SARS-CoV2 infection in seven tertiary-hospitals in Switzerland. Patients were randomly assigned 1:1 to a single intravenous dose of canakinumab (body weight adapted dose of 450-750 mg) or placebo. Canakinumab and placebo were compared based on an unmatched win-ratio approach based on length of survival, ventilation, ICU stay and hospitalization at day 29. This study is registered with ClinicalTrials.gov, NCT04510493. Findings: Between October 17, 2020, and May 12, 2021, 116 patients were randomly assigned with 58 in each group. One participant dropped out in each group for the primary analysis. At the time of randomization, 85 patients (74·6 %) were treated with dexamethasone. The win-ratio of canakinumab vs placebo was 1·08 (95 % CI 0·69-1·69; p = 0·72). During four weeks, in the canakinumab vs placebo group 4 (7·0%) vs 7 (12·3%) participants died, 11 (20·0 %) vs 16 (28·1%) patients were on ICU, 12 (23·5 %) vs 11 (21·6%) were hospitalised for more than 3 weeks, respectively. Median ventilation time at four weeks in the canakinumab vs placebo group was 10 [IQR 6.0, 16.5] and 16 days [IQR 14.0, 23.0], respectively. There was no statistically significant difference in HbA1c after four weeks despite a lower number of anti-diabetes drug administered in patients treated with canakinumab. Finally, high-sensitive CRP and IL-6 was lowered by canakinumab. Serious adverse events were reported in 13 patients (11·4%) in each group. Interpretation: In patients with type 2 diabetes who were hospitalised with COVID-19, treatment with canakinumab in addition to standard-of-care did not result in a statistically significant improvement of the primary composite outcome. Patients treated with canakinumab required significantly less anti-diabetes drugs to achieve similar glycaemic control. Canakinumab was associated with a prolonged reduction of systemic inflammation. Funding: Swiss National Science Foundation grant #198415 and University of Basel. Novartis supplied study medication.

Comparison of temporal evolution of computed tomography imaging features in COVID-19 and influenza infections in a multicenter cohort study.

Purpose: To compare temporal evolution of imaging features of coronavirus disease 2019 (COVID-19) and influenza in computed tomography and evaluate their predictive value for distinction. Methods: In this retrospective, multicenter study 179 CT examinations of 52 COVID-19 and 44 influenza critically ill patients were included. Lung involvement, main pattern (ground glass opacity, crazy paving, consolidation) and additional lung and chest findings were evaluated by two independent observers. Additional findings and clinical data were compared patient-wise. A decision tree analysis was performed to identify imaging features with predictive value in distinguishing both entities. Results: In contrast to influenza patients, lung involvement remains high in COVID-19 patients > 14 days after the diagnosis. The predominant pattern in COVID-19 evolves from ground glass at the beginning to consolidation in later disease. In influenza there is more consolidation at the beginning and overall less ground glass opacity (p = 0.002). Decision tree analysis yielded the following: Earlier in disease course, pleural effusion is a typical feature of influenza (p = 0.007) whereas ground glass opacities indicate COVID-19 (p = 0.04). In later disease, particularly more lung involvement (p < 0.001), but also less pleural (p = 0.005) and pericardial (p = 0.003) effusion favor COVID-19 over influenza. Regardless of time point, less lung involvement (p < 0.001), tree-in-bud (p = 0.002) and pericardial effusion (p = 0.01) make influenza more likely than COVID-19. Conclusions: This study identified differences in temporal evolution of imaging features between COVID-19 and influenza. These findings may help to distinguish both diseases in critically ill patients when laboratory findings are delayed or inconclusive.

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.

Distribution of Aspergillus Species and Prevalence of Azole Resistance in Respiratory Samples From Swiss Tertiary Care Hospitals.

Among 400 Aspergillus species from respiratory samples in Switzerland, Aspergillus fumigatus was the most frequent species. Non-fumigatus Aspergillus spp were more prevalent among solid organ transplant recipients and after azole exposure. Azole resistance was detected in 4 A fumigatus isolates, 3 of them with the "environmental" mutation TR34/L98H in the cyp51A gene.

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.

Antibiotic prophylaxis with amoxicillin to prevent infective endocarditis in periodontitis patients reconsidered: a narrative review.

OBJECTIVES: To discuss first, the adequacy of the antibiotic prophylaxis regimen currently recommended for the prevention of infective endocarditis in periodontitis patients, and second, preventive measures to decrease the rate of bacteraemia after periodontal treatment. MATERIALS AND METHODS: A bibliographic literature search identifying clinical trials between January 1990 and January 2021, focusing on microorganisms in bacteraemia after periodontal treatment and bacteria in infective endocarditis, was performed. Two reviewers independently identified and screened the literature by systematically searching in Medline/Premedline, EMBASE and Cochrane Library. RESULTS: Two hundred and seventy articles were identified, of which twenty-three met the inclusion criteria. Bacteraemia rates after periodontal treatment ranged from 10-94% in the investigated patients. Mainly oral pathogens related to infective endocarditis, such as viridans group streptococci (up to 70%) and HACEK group pathogens (e.g., Aggregatibacter actinomycetemcomitans), were detected. But typical oral and periodontopathogenic species, such as Porphyromonas spp. (P.s gingivalis) (up to 50%), Actinomyces spp. (up to 30%) and Fusobacterium spp. (up to 30%), which do not usually cause infective endocarditis, were also found. Infective endocarditis episodes that might have been in association with a dental treatment were mainly caused by viridans group streptococci. Prophylactic measures like rinse application of chlorhexidine, povidone-iodine or essential oils, diode laser or systemic antibiotic prescription were described as decreasing the bacteraemia rate after periodontal interventions to 5-70%. CONCLUSION: The currently recommended systemic antibiotic prophylaxis with amoxicillin before periodontal treatment in high-risk cardiovascular patients still covers the most common oral bacteria causing infective endocarditis, namely viridans group streptococci, and therefore seems adequate in this context. Since bacteraemia, not infective endocarditis, is the endpoint in most studies, the causality between bacteraemia after periodontal treatments and infective endocarditis remains difficult to elucidate. Until more evidence is available regarding this, adherence to current guidelines for antibiotic prophylaxis in patients at high risk for infective endocarditis undergoing periodontal treatment remains recommended.

Trends of the Epidemiology of Candidemia in Switzerland: A 15-Year FUNGINOS Survey.

BACKGROUND: The increasing incidence of candidemia and emergence of drug-resistant Candida species are major concerns worldwide. Long-term surveillance studies are needed. METHODS: The Fungal Infection Network of Switzerland (FUNGINOS) conducted a 15-year (2004-2018), nationwide, epidemiological study of candidemia. Hospital-based incidence of candidemia, Candida species distribution, antifungal susceptibility, and consumption were stratified in 3 periods (2004-2008, 2009-2013, 2014-2018). Population-based incidence over the period 2009-2018 derived from the Swiss Antibiotic Resistance Surveillance System (ANRESIS). RESULTS: A total of 2273 Candida blood isolates were studied. Population and hospital-based annual incidence of candidemia increased from 2.96 to 4.20/100 000 inhabitants (P = .022) and 0.86 to 0.99/10 000 patient-days (P = .124), respectively. The proportion of Candida albicans decreased significantly from 60% to 53% (P = .0023), whereas Candida glabrata increased from 18% to 27% (P < .0001). Other non-albicans Candida species remained stable. Candida glabrata bloodstream infections occurred predominantly in the age group 18-40 and above 65 years. A higher proportional increase of C glabrata was recorded in wards (18% to 29%, P < .0001) versus intensive care units (19% to 24%, P = .22). According to Clinical and Laboratory Standards Institute, nonsusceptibility to fluconazole in C albicans was observed in 1% of isolates, and anidulafungin and micafungin nonsusceptibility was observed in 2% of C albicans and C glabrata. Fluconazole consumption, the most frequently used antifungal, remained stable, whereas use of mold-active triazoles and echinocandins increased significantly in the last decade (P < .0001). CONCLUSIONS: Over the 15-year period, the incidence of candidemia increased. A species shift toward C glabrata was recently observed, concurring with increased consumption of mold-active triazoles.

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.

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.

Ophthalmic Screening in Patients with Coronavirus Disease 2019: A Prospective Cohort Study.

Postmortem pathological examinations, animal studies, and anecdotal reports suggest that coronavirus disease 2019 (COVID-19) could potentially affect intraocular tissue. However, published evidence is scarce and conflicting. In our study, we screened 100 eyes of 50 patients hospitalized for COVID-19. Relevant medical and ophthalmological history was assessed as well as symptoms, laboratory results, specific treatments, clinical course, and outcome. Ophthalmic exams including assessment of best corrected visual acuity (BCVA), intraocular pressure (IOP), color perception, ocular motility, ophthalmoscopy as well as optical coherence tomography (OCT) of the macula and the optic disc was performed at hospital admission and 29 to 192 days later. Of the 50 patients included, 14 (28%) were female. Median age was 64.5 (range 29-90) years. COVID-19 severity was mild in 15 (30%), severe in 30 (60%), and critical in five cases (10%). At baseline, median BCVA was 0.1 (0-1.8) Logarithm of the Minimum Angle of Resolution (LogMAR) and median IOP was 16 (8-22) mmHg. At follow-up, no relevant changes in BCVA and IOP were documented. No signs of active intraocular inflammation or optic nerve affection were found and OCT findings were widely stable during the observation period. Our findings suggest that COVID-19 does not regularly affect intraocular tissue.

Data linkage to evaluate the long-term risk of HIV infection in individuals seeking post-exposure prophylaxis.

Evidence on the long-term risk of HIV infection in individuals taking HIV post-exposure prophylaxis remains limited. In this retrospective data linkage study, we evaluate the occurrence of HIV infection in 975 individuals who sought post-exposure prophylaxis in a tertiary hospital between 2007 and 2013. Using privacy preserving probabilistic linkage, we link these 975 records with two observational databases providing data on HIV events (Zurich Primary HIV Infection study and the Swiss HIV Cohort Study). This enables us to identify 22 HIV infections and to obtain long-term follow-up data, which reveal a median of 4.1 years between consultation for post-exposure prophylaxis and HIV diagnosis. Even though men who have sex with men constitute only 35.8% of those seeking post-exposure prophylaxis, all 22 events occur in this subgroup. These findings should strongly encourage early consideration of pre-exposure prophylaxis in men who have sex with men after a first episode of post-exposure prophylaxis.

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.

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.

Lung Assessment with Point-of-Care Ultrasound in Respiratory Coronavirus Disease (COVID-19): A Prospective Cohort Study.

Lung ultrasound (LUS) has shown promising diagnostic potential in different pulmonary conditions. We evaluated the diagnostic accuracy of LUS for pulmonary COVID-19. In this prospective cohort study at a Swiss tertiary care center, patients hospitalized with suspected COVID-19 were scanned using a 12-zone protocol. Association of a summation score (0-36 points) with the final diagnosis was tested using the area under the receiver operating characteristic curve and sensitivity and specificity at different cutoff points. Of the 49 participants, 11 (22%) were later diagnosed with COVID-19. LUS score showed excellent diagnostic performance, with an odds ratio of 1.30 per point (95% confidence interval [CI], 1.09-1.54, p = 0.003) and an area under the curve of 0.85 (95% CI, 0.71-0.99). At a cutoff of 8/36 points, 10 of 11 participants later diagnosed with COVID-19 were correctly predicted (sensitivity 91%, 95% CI, 59%-100%), and 29 of the 38 who were not diagnosed with COVID-19 were correctly ruled out (specificity 76%, 95% CI, 60%-89%). LUS demonstrated promising discriminatory potential in people hospitalized with suspected COVID-19.