Coronavirus disease 2019 (COVID-19) is primarily a pulmonary disease, but also affects the cardiovascular system in multiple ways. In this review, we will summarise and put into perspective findings and debates relating to the diverse aspects of cardiovascular involvement of COVID-19. We will review evidence for the role of the renin-angiotensin-aldosterone system (RAAS), the risk of pre-existing cardiovascular disease in COVID-19 susceptibility and course, and the mechanism of acute and long-term myocardial injury.
The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) uses membrane-bound angiotensin converting-enzyme-2 (ACE2) as a receptor for cell entry. ACE2 is part of an important counter-regulatory circuit antagonising the harmful effects of angiotensin II on lung and heart. Modulation of ACE2 may therefore affect disease susceptibility and disease course. However, observational clinical studies and one randomised trial have so far not yielded evidence for harmful or beneficial effects of blockers of the RAAS during COVID-19. Age, gender, and multi-morbidity all increase susceptibility to SARS-CoV-2. In contrast, pre-existing cardiovascular diseases do so only minimally, but they may aggravate the disease course.
Direct SARS-CoV-2 infection of the heart tissue and myocytes is rare. Nevertheless, COVID-19 may lead to myocarditis-like acute cardiac injury, characterised by myocardial oedema, but lacking extensive myocyte loss and lymphocytic infiltration. Independent of this, increases in cardiac biomarkers (troponin, N-terminal pro-brain natriuretic peptide, D-dimer) are frequent, especially in the phase of severe systemic inflammation and acute respiratory distress syndrome, and quantitatively associated with poor outcome. The pulmonary infection may result initially in right ventricular dysfunction, but in cases with severe systemic infection hypoxia, hyperinflammation and cytokine storm heart failure may eventually ensue.
Unlike other infections and inflammatory states, COVID-19 does not appear to trigger acute coronary syndromes. In children, even mild COVID-19 can induce a multisystem inflammatory syndrome with Kawasaki-like symptoms frequently accompanied by cardiogenic shock.
INTRODUCTION
Emicizumab (Hemlibra®, Hoffmann-La Roche, Switzerland) is now available for haemophilia A patients with or without factor VIII inhibitors. Management of bleeding events and replacement therapy for invasive procedures have to be adapted.
OBJECTIVETo provide a practical guidance for the management of breakthrough bleeding events and elective or urgent surgery in adult and paediatric patients with haemophilia A without inhibitors treated with emicizumab.
METHODSBased on the available literature and the experiences collected from adult and paediatric patients treated in Switzerland, the Working Party on Haemostasis of the Swiss Society of Haematology and the Swiss Haemophilia Network worked together to reach a consensus on the management of bleeding events and invasive procedures.
RESULTS AND CONCLUSIONMinor bleeding events and invasive procedures associated with low bleeding risk can be treated without factor replacement therapy in most cases, whereas major bleeding events and high-risk surgery require additional factor VIII replacement at usual doses, at least for the first days. Emicizumab treatment should be continued throughout the procedure and during the postoperative period. Elective major surgery should be planned according to emicizumab dosing for patients with a once-a-month posology. Of note, so far only few data are available on the management of major bleeds and surgery in patients with haemophilia A treated with emicizumab and this practical guidance will have to be regularly updated with growing experience.
AIMS OF THE STUDY
Hydroxychloroquine and lopinavir/ritonavir have been used as experimental therapies to treat COVID-19 during the first wave of the pandemic. Randomised controlled trials have recently shown that there are no meaningful benefits of these two therapies in hospitalised patients. Uncertainty remains regarding the potential harmful impact of these therapies as very early treatments and their burden to the health care system. The present study investigated the length of hospital stay (LOS), mortality, and costs of hydroxychloroquine, lopinavir/ritonavir or their combination in comparison with standard of care among patients hospitalised for coronavirus disease 2019 (COVID-19).
METHODSThis retrospective observational cohort study took place in the Geneva University Hospitals, Geneva, Switzerland (n = 840) between 26 February and 31 May 2020. Demographics, treatment regimens, comorbidities, the modified National Early Warning Score (mNEWS) on admission, and contraindications to COVID-19 treatment options were assessed. Outcomes included LOS, in-hospital mortality, and drug and LOS costs.
RESULTSAfter successful propensity score matching, patients treated with (1) hydroxychloroquine, (2) lopinavir/ritonavir or (3) their combination had on average 3.75 additional hospitalisation days (95% confidence interval [CI] 1.37–6.12, p = 0.002), 1.23 additional hospitalisation days (95% CI −1.24 – 3.51, p = 0.319), and 4.19 additional hospitalisation days (95% CI 1.52–5.31, p <0.001), respectively, compared with patients treated with the standard of care. Neither experimental therapy was significantly associated with mortality. These additional hospital days amounted to 1010.77 additional days for hydroxychloroquine and hydroxychloroquine combined with lopinavir/ritonavir, resulting in an additional cost of US$ 2,492,214 (95%CI US$ 916,839–3,450,619).
CONCLUSIONSPrescribing experimental therapies for COVID-19 was not associated with a reduced LOS and might have increased the pressure put on healthcare systems.
AIM
To assess the impact of the first wave of the COVID-19 pandemic on acute coronary syndromes and on the delay from symptom onset to first medical contact among patients presenting with ST-segment elevation myocardial infarction (STEMI), as well as to investigate whether there were patient-related reasons related to COVID-19 for delaying first medical contact.
METHODS AND RESULTSAll patients undergoing percutaneous coronary intervention (PCI) at the Geneva University Hospitals for acute coronary syndromes (ACS) during the first COVID-19 wave were compared with a control group consisting of all ACS patients who underwent PCI during the same period in 2019 and those treated in the period immediately preceding the pandemic. The primary outcome measure was the difference in the delay from symptom onset to first medical contact in the setting of STEMI between the COVID-19 period and the control period. Secondary outcome measures were the difference in ACS incidence and the impact of the COVID-19 pandemic on patients’ decisions to call the emergency services, assessed using a questionnaire. Delay from symptom onset to first medical contact was longer among patients suffering from STEMI in the COVID-19 period compared with the control period (112 min vs 60 min, p = 0.049). The incidence rate of ACS was lower during the COVID-19 period (incidence rate ratio 0.6, 95% confidence interval [CI] 0.449–0.905). ACS patients delayed their call to the emergency services mainly because of fear of contracting or spreading COVID-19 following hospital admission, as well as of adding burden to the healthcare system.
CONCLUSIONWe observed prolonged delays from symptom onset to first medical contact and a decline in overall ACS incidence during the first wave of the COVID-19 pandemic, with a higher threshold to call for help among ACS patients.
AIMS OF THE STUDY
The impact of coronavirus disease 2019 (COVID-19) on patients listed for solid organ transplantation has not been systematically investigated to date. Thus, we assessed occurrence and effects of infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on patients on the Swiss national waiting list for solid organ transplantation.
METHODSPatient data were retrospectively extracted from the Swiss Organ Allocation System (SOAS). From 16 March to 31 May 2020, we included all patients listed for solid organ transplantation on the Swiss national waiting list who were tested positive for SARS-CoV-2. Severity of COVID-19 was categorised as follows: stage I, mild symptoms; stage II, moderate to severe symptoms; stage III, critical symptoms; stage IV, death. We compared the incidence rate (laboratory-confirmed cases of SARS-CoV-2), the hospital admission rate (number of admissions of SARS-CoV-2-positive individuals), and the case fatality rate (number of deaths of SARS-CoV-2-positive individuals) in our study population with the general Swiss population during the study period, calculating age-adjusted standardised incidence ratios and standardised mortality ratios, with 95% confidence intervals (CIs).
RESULTSA total of 1439 patients were registered on the Swiss national solid organ transplantation waiting list on 31 May 31 2020. Twenty-four (1.7%) waiting list patients were reported to test positive for SARS-CoV-2 in the study period. The median age was 56 years (interquartile range 45.3–65.8), and 14 (58%) were male. Of all patients tested positive for SARS-CoV-2, two patients were asymptomatic, 14 (58%) presented in COVID-19 stage I, 3 (13%) in stage II, and 5 (21%) in stage III. Eight patients (33%) were admitted to hospital, four (17%) required intensive care, and three (13%) mechanical ventilation. Twenty-two patients (92%) of all those infected recovered, but two male patients aged >65 years with multiple comorbidities died in hospital from respiratory failure. Comparing our study population with the general Swiss population, the age-adjusted standardised incidence ratio was 4.1 (95% CI 2.7–6.0).
CONCLUSIONThe overall rate of SARS-CoV-2 infections in candidates awaiting solid organ transplantation was four times higher than in the Swiss general population; however, the frequency of testing likely played a role. Given the small sample size of affected patients, conclusions have to be drawn cautiously and results need verification in larger cohorts.
The systematic identification of infected individuals is critical for the containment of the COVID-19 pandemic. Currently, the spread of the disease is mostly quantified by the reported numbers of infections, hospitalisations, recoveries and deaths; these quantities inform epidemiology models that provide forecasts for the spread of the epidemic and guide policy making. The veracity of these forecasts depends on the discrepancy between the numbers of reported, and unreported yet infectious, individuals. We combine Bayesian experimental design with an epidemiology model and propose a methodology for the optimal allocation of limited testing resources in space and time, which maximises the information gain for such unreported infections. The proposed approach is applicable at the onset and spread of the epidemic and can forewarn of a possible recurrence of the disease after relaxation of interventions. We examine its application in Switzerland; the open source software is, however, readily adaptable to countries around the world. We find that following the proposed methodology can lead to vastly less uncertain predictions for the spread of the disease, thus improving estimates of the effective reproduction number and the future number of unreported infections. This information can provide timely and systematic guidance for the effective identification of infectious individuals and for decision-making regarding lockdown measures and the distribution of vaccines.
Currently, a major focus of biomedical research and clinical application are the so-called advanced therapy medicinal products (ATMPs), which are highly complex medicines that enable the targeted and personalised treatment of patients. The potential of ATMPs in future cancer treatment is invaluable. However, this novel class of treatments is often extremely expensive. Consequently, these therapies push established reimbursement models to their limits. Because of the high costs, as well as the lack of appropriate reimbursement models, access to these potentially lifesaving therapies is currently not guaranteed to all patients. This paper analyses the current legal framework in Switzerland and critically evaluates existing reimbursement models, particularly with respect to their adaptation for ATMPs. As a promising reimbursement arrangement, this paper proposes a model combining outcome-based instalment payments with aspects of the pay for performance and the annuity payment model. According to this performance-based shared risk model, instalment payments are due when defined treatment goals are achieved.
AIMS OF THE STUDY
Chest tubes inserted to drain shed mediastinal blood after cardiac surgery often become clogged, limiting their capacity to evacuate blood, and leading to blood retention and retained blood syndrome. The aim of this study was the assessment of the efficacy of an active tube clearance (ATC) system in the reduction of retained blood syndrome after cardiac surgery.
METHODSThis study included 2461 adult patients undergoing major cardiac surgery. Patients receiving conventional chest tubes only (n = 1980) were compared with patients receiving an ATC tube in the retrosternal position (n = 481) for interventions caused by retained blood syndrome (re-exploration for bleeding or tamponade and interventions for pleural effusion or pneumothorax), kidney replacement therapy, postoperative atrial fibrillation, sternal infection and chest tube output before and after propensity score matching.
RESULTSPropensity score matching generated 471 patient-pairs balanced for their baseline characteristics. Matched patients with an ATC tube in the retrosternal position had no statistically significant difference in the rate of intervention for retained blood syndrome (33% vs 31%, p = 1), re-exploration because of bleeding or tamponade (2.5% vs 4%, p = 1), intervention for pneumothorax (4.7% vs 4.9%, p = 1) and intervention for pleural effusion (28% vs 28%, p = 1), but had statistically significantly less chest tube output on the first postoperative day (median 480, IQR 316–700 ml vs median 590, IQR 380–905 ml; p <0.0001) and second postoperative day (median 505, IQR 342–800 ml vs median 597, IQR 383–962 ml; p = 0.0012) in comparison with patients with conventional chest tubes only.
CONCLUSIONAn ATC tube in the retrosternal position reduced chest tube output but showed no reduction in the rate of intervention for retained blood syndrome. Further research should be performed to test the combination of ATC in the retrosternal and the inferior pericardial space.
AIMS OF THE STUDY
The Cancer Registry Zurich, Zug, Schaffhausen and Schwyz is one of the oldest cancer registries in Switzerland, first registering tumours in 1980 for the canton of Zurich. The aim of this study was to analyse trends in incidence and mortality for the most common types of cancer in the canton of Zurich from 1981 to 2017.
METHODSIn this analysis of population-based cancer registry data, we included malignant tumours of the breast (ICD10 C50), prostate (C61), colon/rectum (C18–C21), lung (C33–C34), and melanoma (C43), diagnosed between 1981 and 2017. Age-standardised incidence and mortality rates per 100,000 person-years were computed using the 1976 European Standard Population. Incidence and mortality time trends were assessed using joinpoint regression analysis.
RESULTSIn men, incidence for prostate cancer and melanoma increased over the study period, while it decreased for colon/rectum and lung cancer. A joinpoint for prostate cancer indicated the start of a decreasing trend in 2002. In women, incidence increased for breast cancer, lung cancer and melanoma; no trend was observed for colon/rectum cancer. Cancer mortality decreased for prostate, colon/rectum and lung cancer in men, with no clear trend for melanoma. In women, mortality decreased for breast cancer, colon/rectum cancer and melanoma, but increased for lung cancer.
CONCLUSIONSThe overall increasing incidence trends for prostate and breast cancer, as well as for melanoma, are in line with data from other Western countries. While lung cancer incidence is decreasing in men, it is still on the rise in women. Despite increasing incidence rates, mortality rates are decreasing for all localisations except for lung cancer in women. The opposite direction of incidence and mortality curves is probably mostly due to better and more effective treatment options, as well as earlier detection.
OBJECTIVES
In Switzerland, universal health insurance does not cover any routine testing for sexually transmitted infections (STIs), not even in individuals at high risk, and extra-genital swabbing is not standard of care. We compared STI prevalence in a multicentre prospective observational cohort of multi-partner women with/without sex work and evaluated associated risk factors.
MATERIALS AND METHODSBetween January 2016 and June 2017, we offered free STI testing to women with multiple sexual partners (three or more in the previous 12 months), with follow-up examinations every 6 months. We used multiplex polymerase chain-reaction testing (for Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis, Mycoplasma genitalium) for pooled swabs (pharynx, urethra/vagina, anus), and antibody tests for human immunodeficiency virus (HIV) and Treponema pallidum at every visit, and for hepatitis B and C at baseline.
RESULTSWe screened 490 female sex workers (FSWs), including 17 trans women, and 92 other multi-partner women. More than half reported a steady partner. Previously undiagnosed HIV was found in 0.2% vs 0.0%, respectively, and T. pallidum antibodies in 5.9% vs 0.0%. STIs requiring antibiotic treatment comprised: active syphilis 1.2% vs 0.0%; N. gonorrhoeae 4.9% vs 0.0%; C. trachomatis 6.3% vs 5.4%, T. vaginalis 10.4% vs 0.0%; M. genitalium 6.7% vs 6.5%. One in four FSWs vs one in nine other women had one or more of these STIs at baseline. 15.8% vs 3.8% had a history of hepatitis B, 45.5% vs 22.8% had no immunity (HBs-AB <10 IU/l). Two FSWs had hepatitis C virus antibodies (0.4%) without concurrent HIV infection. Non-condom-use (last three months) for anal/vaginal sex was not associated with STIs. Independent risk factors were group sex (adjusted odds ratio [aOR] 2.1, 95% confidence interval [CI] 1.1–4.0), age less than 25 (aOR 3.7, 95% CI 1.6–8.9), and being active in sex work for less than 1 year (aOR 2.7, 95% CI 1.3–5.3).
CONCLUSIONHIV and HCV do not appear to pose a major public health problem among FSWs in Switzerland, whereas vaccination against HBV should be promoted. FSWs showed high rates of STIs requiring treatment to reduce transmission to clients and/or steady partners. FSWs should be offered low-cost or free STI screening as a public health priority.
OBJECTIVES
In Switzerland, universal health insurance does not cover any routine testing for sexually transmitted infections (STIs), not even in individuals at high risk, and extra-genital swabbing is not standard of care. We determined the prevalence and incidence of human immunodeficiency virus (HIV), viral hepatitis and non-viral STIs in a multicentre prospective observational cohort of multi-partner men who have sex with men (MSM) and other men.
MATERIALS AND METHODSBetween January 2016 and June 2017, we offered free STI testing to all men with multiple sexual partners (three or more in the previous 12 months), with follow-up examinations every 6 months. We used multiplex polymerase chain-reaction testing (for Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis, Mycoplasma genitalium) on pooled swabs (pharynx, urethra/vagina, anus), and antibody tests for HIV and Treponema pallidum at every visit, and for hepatitis B/C at baseline.
RESULTSWe screened 779 multi-partner MSM and 92 other men. Previously undiagnosed HIV was found in 0.5% vs 0.0%, respectively and T. pallidum antibodies in 15.3% vs 1.1%. STIs requiring antibiotic treatment comprised: active syphilis 1.7% vs 0.0%; N. gonorrhoeae 10.3% vs 0.0%; C. trachomatis 8.7% vs 1.1%. One in four MSM versus 1 in 100 other multi-partner men had any of these three STIs at baseline. 10.4% vs 1.3% had a history of hepatitis B, 31.9% vs 47.3% had no immunity (HBs-AB <10 IU/l). Ten MSM had HCV antibodies (1.4%), with 8 out of the 10 being MSM with HIV; HCV seroprevalence was 0.3% among HIV-negative MSM. In MSM, incidence of the three bacterial STIs was 25.5 per year over 333 person years of follow-up, HIV incidence was 0.3%. Non-condom-use (in the last 3 months) for anal/vaginal sex was not associated with STIs. Independent risk factors were sex with men (adjusted odds ratio [aOR] 16.4) and the number of sexual partners (aOR 2.3 for >20).
CONCLUSIONAmong MSM, but not among other multi-partner men, STIs, mostly asymptomatic, are common. Given the high risk of onward transmission, low-cost or free routine screening of multi-partner MSM is a public health priority.
Female sex workers are often considered highly vulnerable to sexually transmitted infections (STIs). However, data on STI epidemiology in female sex workers are lacking in Switzerland. Our main goal was to evaluate the prevalence of six STIs (human immunodeficiency virus [HIV], hepatitis B, hepatitis C, Chlamydia trachomatis, Neisseria gonorrhoeae and syphilis) among local female sex workers in Lausanne. A local, exploratory, cross-sectional study was conducted on a convenience sample of adult (≥18 years) female sex workers in Lausanne, Switzerland, from 1 April 2015 to 31 December 2016. Female sex workers who worked in street sex venues, massage parlours and brothels were approached for recruitment by a local non-governmental organisation. They were then invited to present at the Lausanne University Hospital, where they were offered a free STI screening and hepatitis A and B vaccination. We enrolled 96 female sex workers. They were predominantly undocumented immigrants (60%) from Africa and Eastern Europe with no health insurance; only one participant (1%) was Swiss born. During the study, 15 (16%; 95% confidence interval [CI] 9–23%) participants were newly confirmed to have an STI: six (6%; 95% CI 1–11%) had C. trachomatis, five (5%; 95% CI 0.6-9%) latent syphilis and four (4%; 95% CI 0.1–8%) hepatitis B (three with chronic active infection and one with past exposure). No human immunodeficiency virus (HIV) infections were newly diagnosed among the participants. Nineteen (20%) of the female sex workers were already vaccinated against hepatitis B, and 73 (76%) initiated vaccination against hepatitis A and hepatitis B during the study. Forty-four (46%) of the female sex workers required translation and assistance from social services.
In the wake of the pandemic of coronavirus disease 2019 (COVID-19), contact tracing has become a key element of strategies to control the spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Given the rapid and intense spread of SARS-CoV-2, digital contact tracing has emerged as a potential complementary tool to support containment and mitigation efforts. Early modelling studies highlighted the potential of digital contact tracing to break transmission chains, and Google and Apple subsequently developed the Exposure Notification (EN) framework, making it available to the vast majority of smartphones. A growing number of governments have launched or announced EN-based contact tracing apps, but their effectiveness remains unknown. Here, we report early findings of the digital contact tracing app deployment in Switzerland. We demonstrate proof-of-principle that digital contact tracing reaches exposed contacts, who then test positive for SARS-CoV-2. This indicates that digital contact tracing is an effective complementary tool for controlling the spread of SARS-CoV-2. Continued technical improvement and international compatibility can further increase the efficacy, particularly also across country borders.
AIMS OF THE STUDY
Coronavirus disease 2019 (COVID-19) pandemic has an ongoing severe impact on health care, but there is a lack of information on COVID-19 and its effect on organ donation and solid organ transplantation. Early in the pandemic, Swisstransplant, the Swiss National Foundation for Organ Donation and Transplantation, set up a national stepwise shutdown approach to avoid a collapse of transplant activities during phases of the pandemic with sufficient available healthcare capacities. The approach allowed regional adaptation of transplant-associated activities depending on available healthcare capacities, instead of implementing a rigid centralistic system. The aim of this study was to describe the stepwise shutdown approach and to determine whether this flexible approach would be helpful for avoiding complete cessation of transplant activities during a pandemic.
METHODSA retrospective nationwide study was conducted to evaluate donor procurement and solid organ transplantation activity in Switzerland during the COVID-19 pandemic (1 January to 31 May 2020). To assess the impact of the flexible stepwise shutdown plan on overall transplantation activity in Switzerland, we compared total and individual numbers of transplanted organs during the first wave of the pandemic with the transplant activity immediately before the pandemic.
RESULTSThe pandemic evolved heterogeneously across Swiss cantons, severely affecting western cantons and the Ticino. Overall, there was a reduction in deceased donor transplants in Switzerland of 16.7% in March and April 2020 (during the pandemic) compared with January and February 2020 (prior to the pandemic), the decline mostly driven by kidney transplants (−27.6%) and to a lesser extent by transplants of vital organs (heart, lungs, liver) (−5.9%). In May 2020, solid organ transplantation activity in Switzerland again exceeded the average of pre-pandemic months (January and February), with 35 transplanted organs, but the increase from April to May 2020 was exclusively driven by liver and kidney transplants.
CONCLUSIONThe Swiss stepwise shutdown approach in organ donation and transplantation helped to maintain a limited national organ procurement and vital organ transplant activity, avoiding a complete nationwide shutdown of organ donation and transplant activity. We therefore propose a flexible shutdown approach that regulates transplant activities dependent on regional healthcare resources rather than uniform centralistic regulations. This approach proved to be especially useful during a regional heterogeneously evolving pandemic.
BACKGROUND
Femoral fracture is a significant major trauma in children and adolescents, sometimes resulting in serious complications. This study aimed to determine the epidemiology of femoral fractures and to define associated injuries and mortality incidence in a pediatric population below 16 years old.
METHODSThe medical records of all patients with a femoral fracture treated in our hospital from 1997–2016 were reviewed retrospectively. Age, gender, mechanism of the trauma, month and season of fracture occurrence, fracture type, associated injuries, and mortality data were collected. Patients were divided into four age groups and compared.
RESULTSThe study included 348 children with 353 femoral fractures. The mean annual prevalence of femoral fracture during the study period was 22.7 per 100,000 children. Except for children less than 1 year old, most fractures occurred in male patients (69%), with a male-to-female ratio of 2.2:1. Road accidents were the most common mechanism at all ages. Femoral fractures were mainly due to low-energy trauma in neonates and infants, to road accidents and low-energy trauma in preschool children, to sports accidents in school-age children, and to road traffic accidents in teenagers. February was the month with the most occurrences of femoral fractures. Winter was the peak season for femoral fractures in children aged <1 year and 6–11 years (37.8% and 46.4% of fractures respectively), whereas autumn was the most common season (29.5%) for preschool children and spring (31.1%) the most common in the teenagers group. Diaphyseal fractures were the most commonly reported lesions in all four age groups, representing 72.3% of all fractures. Only 18 fractures were open (5.1%). Eighty-eight patients (25.3%) presented with associated injuries at admission, 12 presented with Waddell’s triad of injuries, and the mortality rate was calculated to be 1.1% (four cases).
CONCLUSIONThe circumstances of injury and the seasonality of femoral fractures differed significantly depending on the children’s ages. Moreover, the morbidity of femoral fractures in children was closely correlated with associated injuries. (Level of evidence: Level III)
