Showing papers in "Internal and Emergency Medicine in 2020"

Systematic review of the prevalence of current smoking among hospitalized COVID-19 patients in China: could nicotine be a therapeutic option?

Abstract: The effects of smoking on Corona Virus Disease 2019 (COVID-19) are currently unknown. The purpose of this study was to systematically examine the prevalence of current smoking among hospitalized patients with COVID-19 in China, considering the high-population smoking prevalence in China (26.6%). A systematic review of the literature (PubMed) was performed on April 1. Thirteen studies examining the clinical characteristics of hospitalized COVID-19 patients in China and presenting data on the smoking status were found. The pooled prevalence of current smoking from all studies was calculated by random-effect meta-analysis. To address the possibility that some smokers had quit shortly before hospitalization and were classified as former smokers on admission to the hospital, we performed a secondary analysis in which all former smokers were classified as current smokers. A total of 5960 patients were included in the studies identified. The current smoking prevalence ranged from 1.4% (95% CI 0.0-3.4%) to 12.6% (95% CI 10.6-14.6%). An unusually low prevalence of current smoking was observed from the pooled analysis (6.5%, 95% CI 4.9-8.2%) as compared to population smoking prevalence in China. The secondary analysis, classifying former smokers as current smokers, found a pooled estimate of 7.3% (95% CI 5.7-8.9%). In conclusion, an unexpectedly low prevalence of current smoking was observed among patients with COVID-19 in China, which was approximately 1/4th the population smoking prevalence. Although the generalized advice to quit smoking as a measure to reduce health risk remains valid, the findings, together with the well-established immunomodulatory effects of nicotine, suggest that pharmaceutical nicotine should be considered as a potential treatment option in COVID-19.

Utilization of machine-learning models to accurately predict the risk for critical COVID-19.

Abstract: Among patients with Coronavirus disease (COVID-19), the ability to identify patients at risk for deterioration during their hospital stay is essential for effective patient allocation and management To predict patient risk for critical COVID-19 based on status at admission using machine-learning models Retrospective study based on a database of tertiary medical center with designated departments for patients with COVID-19 Patients with severe COVID-19 at admission, based on low oxygen saturation, low partial arterial oxygen pressure, were excluded The primary outcome was risk for critical disease, defined as mechanical ventilation, multi-organ failure, admission to the ICU, and/or death Three different machine-learning models were used to predict patient deterioration and compared to currently suggested predictors and to the APACHEII risk-prediction score Among 6995 patients evaluated, 162 were hospitalized with non-severe COVID-19, of them, 25 (154%) patients deteriorated to critical COVID-19 Machine-learning models outperformed the all other parameters, including the APACHE II score (ROC AUC of 092 vs 079, respectively), reaching 880% sensitivity, 927% specificity and 920% accuracy in predicting critical COVID-19 The most contributory variables to the models were APACHE II score, white blood cell count, time from symptoms to admission, oxygen saturation and blood lymphocytes count Machine-learning models demonstrated high efficacy in predicting critical COVID-19 compared to the most efficacious tools available Hence, artificial intelligence may be applied for accurate risk prediction of patients with COVID-19, to optimize patients triage and in-hospital allocation, better prioritization of medical resources and improved overall management of the COVID-19 pandemic

The SARS-CoV-2 receptor, ACE-2, is expressed on many different cell types: implications for ACE-inhibitor- and angiotensin II receptor blocker-based cardiovascular therapies.

Abstract: SARS-CoV-2 is characterized by a spike protein allowing viral binding to the angiotensin-converting enzyme (ACE)-2, which acts as a viral receptor and is expressed on the surface of several pulmonary and extra-pulmonary cell types, including cardiac, renal, intestinal and endothelial cells. There is evidence that also endothelial cells are infected by SARS-COV-2, with subsequent occurrence of systemic vasculitis, thromboembolism and disseminated intravascular coagulation. Those effects, together with the “cytokine storm” are involved in a worse prognosis. In clinical practice, angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin II receptor blockers (ARBs) are extensively used for the treatment of hypertension and other cardiovascular diseases. In in vivo studies, ACE-Is and ARBs seem to paradoxically increase ACE-2 expression, which could favour SARS-CoV-2 infection of host’s cells and tissues. By contrast, in patients treated with ACE-Is and ARBs, ACE-2 shows a downregulation at the mRNA and protein levels in kidney and cardiac tissues. Yet, it has been claimed that both ARBs and ACE-Is could result potentially useful in the clinical course of SARS-CoV-2-infected patients. As detected in China and as the Italian epidemiological situation confirms, the most prevalent comorbidities in deceased patients with COVID-19 are hypertension, diabetes and cardiovascular diseases. Older COVID-19-affected patients with cardiovascular comorbidities exhibit a more severe clinical course and a worse prognosis, with many of them being also treated with ARBs or ACE-Is. Another confounding factor is cigarette smoking, which has been reported to increase ACE-2 expression in both experimental models and humans. Sex also plays a role, with chromosome X harbouring the gene coding for ACE-2, which is one of the possible explanations of why mortality in female patients is lower. Viral entry also depends on TMPRSS2 protease activity, an androgen dependent enzyme. Despite the relevance of experimental animal studies, to comprehensively address the question of the potential hazards or benefits of ACE-Is and ARBs on the clinical course of COVID-19-affected patients treated by these anti-hypertensive drugs, we will need randomized human studies. We claim the need of adequately powered, prospective studies aimed at answering the following questions of paramount importance for cardiovascular, internal and emergency medicine: Do ACE-Is and ARBs exert similar or different effects on infection or disease course? Are such effects dangerous, neutral or even useful in older, COVID-19-affected patients? Do they act on multiple cell types? Since ACE-Is and ARBs have different molecular targets, the clinical course of SARS-CoV-2 infection could be also different in patients treated by one or the other of these two drug classes. At present, insufficient detailed data from trials have been made available.

Clinical features of 1487 COVID-19 patients with outpatient management in the Greater Paris: the COVID-call study.

Abstract: Clinical features of COVID-19 have been mostly described in hospitalized patients with and without ICU admission. Yet, up to 80% of patients are managed in an outpatient setting. This population is poorly documented. In France, health authorities recommend outpatient management of patients presenting mild-to-moderate COVID-19 symptoms. The aim of this study was to describe their clinical characteristics. The study took place in an emergency medical dispatching center located in the Greater Paris region. Patients included in this survey met confirmed COVID-19 infection criteria according to the WHO definition. We investigated clinical features and classified symptoms as general, digestive, ear-nose-throat, thoracic symptoms, and eye disease. Patients were included between March 24 and April 6 2020. 1487 patients included: 700 (47%) males and 752 (51%) females, with a median age of 44 (32-57) years. In addition to dry cough and fever reported in more than 90% of cases, the most common symptoms were general symptoms: body aches/myalgia (N = 845; 57%), headache (N = 824; 55%), and asthenia (N = 886; 60%); shortness of breath (N = 479; 32%) and ear-nose-throat symptoms such as anosmia (N = 415; 28%) and ageusia (N = 422; 28%). Chest pain was reported in 320 (21%) cases and hemoptysis in 41 (3%) cases. The main difference between male and female patients was an increased prevalence of ear-nose-throat symptoms as well as diarrhea, chest pains, and headaches in female patients. General symptoms and ear-nose-throat symptoms were predominant in COVID-19 patients presenting mild-to-moderate symptoms. Shortness of breath and chest pain were remarkably frequent.

Camostat mesilate therapy for COVID-19.

Abstract: Novel coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global threat. Antivirals and vaccines need to be developed to control the disease. This not only entails a considerable expense, it would also take some time for a newly developed drug to be tested for safety and, in the meantime, several more deaths would be inevitable. Under these exigent conditions, the administration of the already developed safe drugs should be the smartest shortcut. TMPRSS2 is a serine protease that primes the spike protein of highly pathogenic human coronaviruses, such as severe acute respiratory syndrome-related coronavirus (SARS-CoV) and Middle East respiratory syndromerelated coronavirus (MERS-CoV), and facilitates its entry into the host cell. Camostat mesilate (CM), an inhibitor of TMPRSS2, blocked the spread and pathogenesis of SARSCoV in a pathogenic mouse model and would be expected to show similar effect in MERS-CoV [1, 2]. Hoffmann et al. determined that the SARS-CoV-2 requires TMPRSS2 [3]. Furthermore, using a sample of SARS-CoV-2 virus isolated from a patient, they found that CM blocks the entry of the virus into the lung cells. CM was developed in Japan as a protease inhibitor in the 1980s and because most of the studies on this compound have been published in Japanese, very little information is available outside of Japan. In Japan, CM therapy for acute symptoms of chronic pancreatitis is covered by health insurance since 1985, and it has also been used to treat postoperative reflux esophagitis since 1994; the oral doses used in these cases are 600 and 300 mg/day, respectively. In a multi-centre, double-blind study on 189 subjects, 3% of the subjects in the group administered 900 mg CM daily for 8 weeks showed side effects (oedema and urticaria); however, there were no side effects over the 8 weeks period in the groups that received a daily CM dose less than 600 mg [4]. In the recent years in Japan, the number of people taking CM for 1 year is estimated to be about 100,000, where only one case of acute eosinophilic pneumonia by CM was reported in 2016 [5]. This case was of a 75-year-old man, where pulmonary infiltration with peripheral blood eosinophilia appeared after taking CM for 10 days. The cause is presumed to be an allergic reaction. His temperature decreased and blood eosinophilia and pulmonary involvements were improved 2 weeks later with the cessation of the drug. However, bilateral ground-glass opacities were temporarily detected on chest CT. Since this CT finding is similar to COVID-19 pneumonia, one must be aware of elevated peripheral blood eosinophilia when using CM for COVID19 treatment. In an experiment on a mouse model, CM was effective in protecting the mice against death, following a lethal SARSCoV infection, with a survival rate of 60% [2]. In this study, the weights of mice were not described, but the average weight was estimated to be approximately 20 g considering the fact that 6 to 8-week-old female BALB/c mice were used. Assuming the weights of a mouse and an adult human to be 20 g and 60 kg, respectively, the equivalent CM dose for humans would be approximately 2.14 mg/kg. CM has a plasma half-life of 100 min and is almost completely eliminated in 4–5 h. Thus, taking 600 mg (200 mg, three times) of CM daily is expected to reduce the SARS-CoV-2 infection. The biggest advantage of using CM for the treatment of COVID-19 is its low cost (one 100 mg tablet is priced as low as USD 0.10–0.40). This pragmatic treatment has the potential to save the lives of many people, including those belonging to the low-income groups. However, to date, there are no clinical data on the use of the drug in blocking or at least reducing viral spread and pathogenesis of CoVs; therefore, human clinical trials are expected.

Low ADAMTS 13 plasma levels are predictors of mortality in COVID-19 patients.

Abstract: Both arterial and venous thrombotic complications have been reported in patients affected by COVID-19, especially in those critically ill. An emerging body of evidence is supporting our understanding of a so-called Coronavirusassociated coagulopathy (CAC) [1]. From a clinical point of view, in the initial phase of the pandemic, numerous empirical therapeutic strategies have been used, to include the use of heparins (alone or in association), hydroxychloroquine, steroids, immunomodulators, as well as plasma from convalescent patients from COVID-19 [2, 3]. However, data are still limited as these approaches have been reported most of the time in non-controlled studies. Nevertheless, regardless the intrinsic limitations of the available studies, some promising results in improving the clinical outcome, to include the thrombotic complications, have been reported. From a laboratory perspective, few considerations are similarly needed. While aPTT is often prolonged in these patients, it does not seem to be associated with a bleeding tendency but rather to the presence of antiphospholipid antibodies, mainly the lupus anticoagulant [4, 5]. Similarly, albeit modest and inconstant thrombocytopenia, increased (sometimes dramatically high) levels of D-dimer, and slightly prolonged prothrombin time (PT) are commonly observed, the mechanisms supporting the developed of CAC are still elusive [1]. The International Society of Thrombosis and Haemostasis (ISTH) recently published an “interim guidance” aiming to define some characteristics of the CAC [6]. Among others, the ISTH interim guidance highlighted some frequently observed hemostatic alterations in patients with CAC, to include D-dimer usually increased, prothrombin time usually only marginally deranged and platelets count usually within rage or slightly reduced. Those observation are in line with the preliminary observations at the beginning of the pandemic outbreak [6–8]. Critically, the mentioned hemostatic alternations differ from those usually observed during the disseminated intravascular coagulopathy [9, 10]. While discriminating between a consumption coagulopathy vs. a thrombotic microangiopathy might be challenging, the differentiation is crucial for therapeutic purpose. In order to further investigate the CAC, we tested ADAMTS-13 and von Willebrand factor (vWF) plasma levels in 88 consecutive PCR-proven COVID-19 admitted patients (main characteristics detailed in Table 1). Adamts13 activity and von Willebrand antigen (vWF:Ag) measurements were performed using CliA activity assays (HemosIL Acustar ADAMTS13 activity, IL, Lexington, MA, USA). ADAMTS-13 levels were significantly reduced in all COVID-19 patients (CP) when compared to healthy controls (HC) (CP, mean 48.71 ± 18.7%, HC, 108 ± 9.1%; normal value 60–130%). These deranged values are similar to those observed in patients with thrombotic thrombocytopenic purpura (TTP), while ADMTS 13 is not generally reduced during a DIC. Antibodies direct to ADAMTS 13 (assessed by Bethesda assay) were tested in the 25 patients with lowest ADAMTS 13 levels. Both ADAMTS-13 activity and antibodies antiADAMTS-13 were tested on the same sample. No patients were found to have significantly increased levels of * Savino Sciascia savino.sciascia@unito.it

Gastrointestinal symptoms associated with severity of coronavirus disease 2019 (COVID-19): a pooled analysis.

Abstract: The identification of clinical predictors of progression towards severe form is urgently needed to enable risk stratification and optimize resource allocation in coronavirus disease 2019 (COVID-19) pandemic. Recently, gastrointestinal shedding of viral RNA detected in fecal samples has been reported in both children and adults [1, 2]. This may be unsurprising given the high expression of viral host receptor angiotensin converting enzyme 2 (ACE2) in gastrointestinal tract [3]. In a clinical study of 138 COVID-19 patients, Wang et al. reported that 10% experienced gastrointestinal symptoms 1–2 days prior the onset of fever and dyspnea [4]. Therefore, we aim here to explore whether or not patients presenting with abdominal pain, nausea, and vomiting, or diarrhea may be at increased odds of the severe form of COVID-19. We performed an electronic search in Medline (PubMed interface) and the Chinese National China National Knowledge Infrastructure (CNKI) with the keywords “nausea” OR “vomiting” OR “diarrhea” in all fields AND “coronavirus 2019” OR “COVID-19” OR “2019-nCoV” OR “SARSCoV-2”, between 2019 and present time (i.e., March 15, 2020), with no language restrictions. Title, abstract, and of all full text of all identified items were analyzed, and those providing the prevalence of gastrointestinal symptoms in adult (> 18 years of age) COVID-19 patients with clinically validated definition of “severe disease” (i.e., patients needing mechanical ventilation, vital life support, and intensive care unit admission) were included in a pooled analysis. No exclusion criteria were applied. The reference list of all retrieved documents was also hand-searched (through forward and backward citation tracking) for identifying additional eligible studies. Articles in Chinese were screened by a healthcare professional fluent in both Chinese and English. When data describing gastrointestinal symptoms were identified, the article was translated into English to enable data collection. As the data set was limited and included case series, no study risk of bias or publication bias assessment was performed. A pooled analysis was finally performed, encompassing the calculation of odds ratio (OR) and 95% confidence interval of abdominal pain, nausea, and vomiting in COVID19 patients with or without severe disease. The statistical analysis was carried out using MetaXL, software Version 5.3 (EpiGear International Pty Ltd., Sunrise Beach, Australia) with an inverse variance model. The study was carried out in accordance with the declaration of Helsinki and with the term of local legislation. As data were publicly available, no ethics approval was required. After duplicate screening, a total number of 49 documents were initially identified, 37 of which ought to be excluded, because they were review articles (n = 13), did not report data on COVID-19 disease (n = 14), did not provide the prevalence of gastrointestinal symptoms in COVID-19 patients with or without severe disease (n = 7), or used mortality to define patient groups (n = 3). Two additional studies could be identified from the reference list of selected articles. Thus, the pooled analysis finally included 10 studies, * Brandon Michael Henry Brandon.henry@cchmc.org

Early predictors of in-hospital mortality in patients with COVID-19 in a large American cohort

Abstract: Coronavirus disease (COVID-19) has aggressively spread across the United States with numerous fatalities. Risk factors for mortality are poorly described. This was a multicentered cohort study identifying patient characteristics and diagnostic markers present on initial evaluation associated with mortality in hospitalized COVID-19 patients. Epidemiological, demographic, clinical, and laboratory characteristics of survivors and non-survivors were obtained from electronic medical records and a multivariable survival regression analysis was conducted to identify risk factors of in-hospital death. Of 1629 consecutive hospitalized adult patients with confirmed COVID-19 from March 1st thru March 31, 2020, 1461 patients were included in final analysis. 327 patients died during hospitalization and 1134 survived to discharge. Median age was 62 years (IQR 50.0, 74.0) with 56% of hospitalized patients under the age of 65. 47% were female and 63% identified as African American. Most patients (55%) had either no or one comorbidity. In multivariable analysis, older age, admission respiratory status including elevated respiratory rate and oxygen saturation ≤ 88%, and initial laboratory derangements of creatinine > 1.33 mg/dL, alanine aminotransferase > 40 U/L, procalcitonin > 0.5 ng/mL, and lactic acid ≥ 2 mmol/L increased risk of in-hospital death. This study is one of the largest analyses in an epicenter for the COVID-19 pandemic. Older age, low oxygen saturation and elevated respiratory rate on admission, and initial lab derangements including renal and hepatic dysfunction and elevated procalcitonin and lactic acid are risk factors for in-hospital death. These factors can help clinicians prognosticate and should be considered in management strategies.

COVID-19, coagulopathy and venous thromboembolism: more questions than answers.

Abstract: The acute respiratory illnesses caused by severe acquired respiratory syndrome corona Virus-2 (SARS-CoV-2) is a global health emergency, involving more than 8.6 million people worldwide with more than 450,000 deaths. Among the clinical manifestations of COVID-19, the disease that results from SARS-CoV-2 infection in humans, a prominent feature is a pro-thrombotic derangement of the hemostatic system, possibly representing a peculiar clinicopathologic manifestation of viral sepsis. The severity of the derangement of coagulation parameters in COVID-19 patients has been associated with a poor prognosis, and the use of low molecular weight heparin (LMWH) at doses registered for prevention of venous thromboembolism (VTE) has been endorsed by the World Health Organization and by Several Scientific societies. However, some relevant issues on the relationships between COVID-19, coagulopathy and VTE have yet to be fully elucidated. This review is particularly focused on four clinical questions: What is the incidence of VTE in COVID-19 patients? How do we frame the COVID-19 associated coagulopathy? Which role, if any, do antiphospolipid antibodies have? How do we tackle COVID-19 coagulopathy? In the complex scenario of an overwhelming pandemic, most everyday clinical decisions have to be taken without delay, although not yet supported by a sound scientific evidence. This review discusses the most recent findings of basic and clinical research about the COVID-associated coagulopathy, to foster a more thorough knowledge of the mechanisms underlying this compelling disease.

Switch from oral anticoagulants to parenteral heparin in SARS-CoV-2 hospitalized patients.

Abstract: The development of COVID-19 syndrome in anticoagulated patients, and especially their admission to intensive-care units with acute severe respiratory syndrome (SARS-CoV-2), expose them to specific problems related to their therapy, in addition to those associated with the acute viral infection. Patients on VKA hospitalized with SARS-CoV-2 show high instability of PT INR due to the variability of vitamin K metabolism, diet, fasting, co-medications, liver impairment, and heart failure. Patients on DOAC are exposed to under/over treatment caused by significant pharmacological interferences. In consideration of the pharmacological characteristics of oral anticoagulant drugs, the multiple pharmacological interactions due to the treatment of acute disease and the possible necessity of mechanical ventilation with hospitalization in intensive-care units, we suggest replacing oral anticoagulant therapies (VKA and DOAC) with parenteral heparin to avoid the risk of over/under treatment.

Treat all COVID 19-positive patients, but do not forget those negative with chronic diseases.

Abstract: The outbreak of coronavirus disease 2019 (COVID-19) has distressed our working practice. Infectious disease specialists, pneumologists and intensivists were not enough to face the enormous amount of patients that needed hospital care; therefore, many doctors have been recruited from other medical specialties trying to take care of as many patients as possible. The 'call to duty' of such doctors for urgent COVID-19 cases, however, diverted the attention from the care of patients with chronic conditions, which might have been neglected or undervalued. In this extremely difficult time, the standard of care of chronic patients has been reduced and this might have determined an increased rate of complications secondary to undermanagement. Thousands of patients with acute and chronic non-COVID-19 conditions have not accessed specialist care in the last weeks in Italy. Moreover, even those patients who have had scheduled an outpatient visit did not attend it for fear of leaving their home or due to the inability to go. During the pandemic, there was a drastic reduction in the number of hospital admissions for any medical conditions different from COVID-19. Self-presentation to the emergency department (ED) has been discouraged and the patients' own fear of being infected by going to the hospital led to also a significant decrease in ED access. During the lockdown, in San Giuseppe Hospital MultiMedica IRCCS, Milan, the ED admissions dropped from the mean of 2361/month in December 2019-February 2020 to 1102 (- 53%) and 861 (- 63%) in March and April 2020, respectively. For all the above-mentioned reasons, it is possible that some clinical conditions will further progress with a significant increase in morbidity and mortality. To prevent this, it is essential that patients with chronic conditions should be at least monitored and managed with telephone or online health consultation, identifying those who need urgent access to care, prioritizing outpatient visits based on disease severity. Patients with mild conditions could be managed outside the hospital by implementing telemedicine and creating networks of general practitioners who can consult with in-hospital specialists.

Hydroxychloroquine and azithromycin as a treatment of COVID-19.

Abstract: Since the emerging of the new coronavirus disease (COVID19) with its staggering worldwide morbidity and mortality, the scientific community has been placed under extraordinary pressure to find safe and effective treatments, pending the availability of a vaccine. Some authors have focused their attention on the use of hydroxychloroquine, currently used in the prevention and treatment of malaria and chronic inflammatory diseases (lupus erythematosus and rheumatoid arthritis). Preclinical data suggest that hydroxychloroquine has in vitro antiviral activity blocking the entry of the virus into cells, decreasing pH within cells and attenuating cytokine production; this in vitro effect was promising against a bunch of virus (dengue, HIV, chikungunya, Ebola, SARS, and MERS) and recently, scientists have demonstrated its efficacy also against SARS-CoV-2 [1, 2]. The in vivo efficacy of hydroxychloroquine has not yet been assessed, even if several trials are ongoing (ex. trial ORCHID, NCT 04332991) [3]. Despite the lack of standardized evidences, hydroxychloroquine has been adopted by clinicians worldwide in the treatment, and in some cases, even in the prevention of patients with SARS-CoV-2 and it is still used even if some recent observational studies have confuted its usefulness [4]. The Chinese National guidelines and the US Food and Drug Administration for emergency uses have both recommended the off-label adoption of hydroxychloroquine in the treatment of COVID-19. Summary

Impact of COVID-19 pandemic on the clinical activities related to arrhythmias and electrophysiology in Italy: results of a survey promoted by AIAC (Italian Association of Arrhythmology and Cardiac Pacing)

Abstract: COVID-19 outbreak had a major impact on the organization of care in Italy, and a survey to evaluate provision of for arrhythmia during COVID-19 outbreak (March–April 2020) was launched. A total of 104 physicians from 84 Italian arrhythmia centres took part in the survey. The vast majority of participating centres (95.2%) reported a significant reduction in the number of elective pacemaker implantations during the outbreak period compared to the corresponding two months of year 2019 (50.0% of centres reported a reduction of > 50%). Similarly, 92.9% of participating centres reported a significant reduction in the number of implantable cardioverter-defibrillator (ICD) implantations for primary prevention, and 72.6% a significant reduction of ICD implantations for secondary prevention (> 50% in 65.5 and 44.0% of the centres, respectively). The majority of participating centres (77.4%) reported a significant reduction in the number of elective ablations (> 50% in 65.5% of the centres). Also the interventional procedures performed in an emergency setting, as well as acute management of atrial fibrillation had a marked reduction, thus leading to the conclusion that the impact of COVID-19 was disrupting the entire organization of health care, with a massive impact on the activities and procedures related to arrhythmia management in Italy.

Potential new treatment strategies for COVID-19: is there a role for bromhexine as add-on therapy?

Abstract: Of huge importance now is to provide a fast, cost-effective, safe, and immediately available pharmaceutical solution to curb the rapid global spread of SARS-CoV-2. Recent publications on SARS-CoV-2 have brought attention to the possible benefit of chloroquine in the treatment of patients infected by SARS-CoV-2. Whether chloroquine can treat SARS-CoV-2 alone and also work as a prophylactic is doubtful. An effective prophylactic medication to prevent viral entry has to contain, at least, either a protease inhibitor or a competitive virus ACE2-binding inhibitor. Using bromhexine at a dosage that selectively inhibits TMPRSS2 and, in so doing, inhibits TMPRSS2-specific viral entry is likely to be effective against SARS-CoV-2. We propose the use of bromhexine as a prophylactic and treatment. We encourage the scientific community to assess bromhexine clinically as a prophylactic and curative treatment. If proven to be effective, this would allow a rapid, accessible, and cost-effective application worldwide.

Emergency Department and Out-of-Hospital Emergency System (112-AREU 118) integrated response to Coronavirus Disease 2019 in a Northern Italy centre.

Abstract: Since December 2019, the world has been facing the life-threatening disease, named Coronavirus disease-19 (COVID-19), recognized as a pandemic by the World Health Organization. The response of the Emergency Medicine network, integrating “out-of-hospital” and “hospital” activation, is crucial whenever the health system has to face a medical emergency, being caused by natural or human-derived disasters as well as by a rapidly spreading epidemic outbreak. We here report the Pavia Emergency Medicine network response to the COVID-19 outbreak. The “out-of-hospital” response was analysed in terms of calls, rescues and missions, whereas the “hospital” response was detailed as number of admitted patients and subsequent hospitalisation or discharge. The data in the first 5 weeks of the Covid-19 outbreak (February 21–March 26, 2020) were compared with a reference time window referring to the previous 5 weeks (January 17–February 20, 2020) and with the corresponding historical average data from the previous 5 years (February 21–March 26). Since February 21, 2020, a sudden and sustained increase in the calls to the AREU 112 system was noted (+ 440%). After 5 weeks, the number of calls and missions was still higher as compared to both the reference pre-Covid-19 period (+ 48% and + 10%, respectively) and the historical control (+ 53% and + 22%, respectively). Owing to the overflow from the neighbouring hospitals, which rapidly became overwhelmed and had to temporarily close patient access, the population served by the Pavia system more than doubled (from 547.251 to 1.135.977 inhabitants, + 108%). To minimize the possibility of intra-hospital spreading of the infection, a separate “Emergency Department—Infective Disease” was created, which evaluated 1241 patients with suspected infection (38% of total ED admissions). Out of these 1241 patients, 58.0% (n = 720) were admitted in general wards (n = 629) or intensive care unit (n = 91). To allow this massive number of admissions, the hospital reshaped many general ward Units, which became Covid-19 Units (up to 270 beds) and increased the intensive care unit beds from 32 to 60. In the setting of a long-standing continuing emergency like the present Covid-19 outbreak, the integration, interaction and team work of the “out-of-hospital” and “in-hospital” systems have a pivotal role. The present study reports how the rapid and coordinated reorganization of both might help in facing such a disaster. AREU-112 and the Emergency Department should be ready to finely tune their usual cooperation to respond to a sudden and overwhelming increase in the healthcare needs brought about by a pandemia like the current one. This lesson should shape and reinforce the future.

The association between cardiac injury and outcomes in hospitalized patients with COVID-19.

Abstract: In this study, we aimed to assess the association between development of cardiac injury and short-term mortality as well as poor in-hospital outcomes in hospitalized patients with COVID-19. In this prospective, single-center study, we enrolled hospitalized patients with laboratory-confirmed COVID-19 and highly suspicious patients with compatible chest computed tomography features. Cardiac injury was defined as a rise of serum high sensitivity cardiac Troponin-I level above 99th percentile (men: > 26 ng/mL, women: > 11 ng/mL). A total of 386 hospitalized patients with COVID-19 were included. Cardiac injury was present among 115 (29.8%) of the study population. The development of cardiac injury was significantly associated with a higher in-hospital mortality rate compared to those with normal troponin levels (40.9% vs 11.1%, p value < 0.001). It was shown that patients with cardiac injury had a significantly lower survival rate after a median follow-up of 18 days from symptom onset (p log-rank < 0.001). It was further demonstrated in the multivariable analysis that cardiac injury could possibly increase the risk of short-term mortality in hospitalized patients with COVID-19 (HR = 1.811, p-value = 0.023). Additionally, preexisting cardiovascular disease, malignancy, blood oxygen saturation < 90%, leukocytosis, and lymphopenia at presentation were independently associated with a greater risk of developing cardiac injury. Development of cardiac injury in hospitalized patients with COVID-19 was significantly associated with higher rates of in-hospital mortality and poor in-hospital outcomes. Additionally, it was shown that development of cardiac injury was associated with a lower short-term survival rate compared to patients without myocardial damage and could independently increase the risk of short-term mortality by nearly two-fold.

Transjugular intrahepatic portosystemic shunt (TIPS): current indications and strategies to improve the outcomes

Abstract: Transjugular intrahepatic portosystemic shunt (TIPS) represents a very effective treatment of complications of portal hypertension. Established indications to TIPS in cirrhotic patients include portal hypertensive bleeding and refractory ascites. Over the years additional indications have been proposed, such as the treatment of vascular disease of the liver, hepatic hydrothorax, hepatorenal syndrome and bleeding from ectopic varices. Indications under evaluation include treatment of portal hypertension prior to major abdominal surgery and treatment of portal vein thrombosis. In spite of these advances, there are still uncertainties regarding the appropriate workup for patients to be scheduled for TIPS. Moreover, prevention and management of post-TIPS complications including hepatic encephalopathy and heart failure are still suboptimal. These issues are particularly relevant considering aging in TIPS candidates in Western countries. Correct selection of patients is mandatory to prevent complications which may eventually frustrate the good hemodynamic results and worsen the patient's quality of life or even life expectancy. The possible role of small diameter TIPS to prevent post-procedural complications is discussed.

COVID-19: The crucial role of blood coagulation and fibrinolysis.

Abstract: The overflow of studies in the recent literature on COVID-19 often gives provisional or contradictory results and therefore deserves pauses of reflection and reconsideration. In fact, knowledges of pathophysiology of this new disease are still in development and hence originate discussions and interpretations. Regarding the role of blood coagulation and fibrinolysis, these mechanisms should be considered as crucial especially in severe cases. It is proposed to consider two distinct phenotypes of thrombotic manifestations: the current "thromboembolic type" also occurring in other kinds of sepsis, and the diffuse micro-thrombotic type, prevailing in the lungs but sometimes extending to other organs. Both types can induce severe disease and are potentially lethal. The micro-thrombotic pattern, more specific for COVID-19, results from a massive activation of coagulation strictly coupled with a hyper-intense inflammatory and immune reaction. This results in widespread occlusive thrombotic micro-angiopathy with destruction of alveoli and obstructive neoangiogenesis. The involvement of fibrinolysis, often neglected, confers a double faceted process of activation/inhibition, finally conducive to a fibrinolytic shutdown that reinforces persistence of micro-thrombi. Considering these peculiar mechanisms, it seems evident that both prophylactic and therapeutic effects of current anti-thrombotic drugs cannot be taken for granted and need therefore new specific and rigorous controlled trials.

Intravitreal anti-VEGF agents and cardiovascular risk

Abstract: Antagonists of Vascular Endothelial Growth Factor (Anti-VEGF) are widely administered by intravitreal injection for the treatment of ocular pathologies such as Age-related Macular Degeneration, Diabetic Macular Edema, Proliferative Diabetic Retinopathy and occlusion of retinal vessels. Anti-VEGF agents, in particular bevacizumab, were introduced in oncology to inhibit tumor-induced angiogenesis feeding neoplastic tissues. Subsequently, other specific agents were developed for intraocular administration. Whereas systemic administration of anti-VEGF agents in oncology is burdened by increased risk of arterial hypertension and embolism, agents administered for ophthalmic indications are delivered locally into the eye globe in much smaller quantities. Nevertheless, clinical observations have raised the possibility that, even in these conditions, anti-VEGF agents may increase cardiovascular risk in patients who, being elderly and/or diabetic, are intrinsically prone to such events. This paper aims at reviewing the current knowledge on VEGF and its pharmacologic antagonists from mechanistic and side effect points of view, with specific reference to patients with sight-threatening conditions. Internists should be aware of the need to collaborate with ophthalmologists and pharmacovigilance operators to define as best as possible the risk/benefit balance of intravitreal agents in patients who might lose their sight if left untreated, or increase their risk of suffering a cardiovascular event if treated.

Protective role of statins in COVID 19 patients: importance of pharmacokinetic characteristics rather than intensity of action.

Abstract: Statins represent a family of drugs that are potentially able to defend COVID-19 patients against uncontrolled systemic inflammatory response produced by the virus Sars-Cov-2. Therefore, some physicians proposed and used anti‐inflammatory agents in the treatment regimen of patients with COVID-19 [1]. Statins are well known for their anti‐inflammatory effects [2], and some hospitals included them in the COVID-19 treatment protocol [3]. In addition, studies in vitro verified that “there is evidence suggesting that statins exert anti-viral activity and may block the infectivity of enveloped viruses” [4]. In other words, statins could be efficient SARS-CoV-2 inhibitors of the main protease, a key coronavirus enzyme, which is a potential drug target [4]. Considering the above premises, we hypothesized that patients taking statins were better protected against mortality risk than those who do not take statins. We verified this hypothesis in a population of 71 consecutive patients with a pre-existing chronic cardiovascular disease, who become ill from COVID-19 between February 29, 2020, and May 20, 2020. The follow-up ended on June 15, 2020. The only endpoint of the study was all-cause mortality. Continuous variables were expressed as mean ± one SD or median (range) values; and categorical data as percentages. All dichotomous variables were compared utilizing the χ2 test; and continuous parameters using analysis of variance (ANOVA) or Mann–Whitney U test, as appropriate. Survival probabilities were estimated with the Kaplan–Meier method and survival curves plotted and compared between groups using the log-rank test. P < 0.05 was considered statistically significant. The baseline characteristics of the studied population were illustrated in Table 1. Groups were created according to the assumption, or not, of statins. The mortality rate of patients taking statins resulted in 21.4% (9 of 42 patients died during the observation period in this group), while in the group of patients without statins it was 34.5% (10 of 29 patients); p < 0.05. The comparison of the survival curves showed a statistically not significant difference (Fig. 1a). In other words, there is a trend towards a reduction in mortality risk, but the effect of statins seems substantially not significant. As a further analysis, to investigate whether the intensity of action of statins could influence the risk of mortality, we divided our 42 patients taking statins into two subgroups, based on the drug’s intensity of action, according to the ACC/AHA Classification [5]. The results were that 18 patients of 42 assumed a high-intensity statin (8 patients of these rosuvastatin 20 mg/die; 8 patients atorvastatin 40 mg/die; and 2 patients atorvastatin 80 mg/die), and 24 patients/42 a lowor moderate-intensity statin (6 patients rosuvastatin 10 mg/die; 2 patients pravastatin 40 mg/die; 2 patients atorvastatin 10 mg/die; 4 patients simvastatin 20 mg/die; and 14 patients atorvastatin 20 mg/die). In the subgroup of high-intensity statins, 4 patients of 18 (22.2%) died, with respect to 6 patients of 24 (25.0%) in the lowmoderate-intensity group. The comparison between the survival curves, in contrast to patients who did not take statins, showed no significant differences (Fig. 1b). To demonstrate whether the pharmacokinetic characteristics of statins were able to determine cardiovascular protection, we divided our 42 patients taking statins into two subgroups, based on the solubility of the used statin. The result was that 16 patients of 42 (38.1%) took a watersoluble (hydrophilic) statin (rosuvastatin in 14 patients and pravastatin in 2), while 26/42 (61.9%) a lipid-soluble (lipophilic) statin (atorvastatin in 22 patients, and simvastatin in 4). The comparison between the survival curves, in contrast to patients who did not take statins, indicated a significant * Rosario Rossi rosario.rossi@unimore.it

WhatsApp and other messaging apps in medicine: opportunities and risks

Abstract: WhatsApp is a popular messaging application frequently used by physicians and healthcare organizations that can improve the continuity of care and facilitate effective health services provision, especially in acute settings. However WhatsApp does not comply with the rules of the European GDPR and the US HIPA Act. So it is inappropriate to share clinical information via WhatsApp.For this reason alternatives to Whatsapp are considered. In particular, the features that must have secure messaging apps to be in compliance with GDPR and HIPAA and to protect patient data will be discussed. The aim is to encourage healthcare organizations and physicians to abandon WhatsApp and to adopt one of the many secure messaging apps now available, some of them at no cost.

Plasma from donors recovered from the new Coronavirus 2019 as therapy for critical patients with COVID-19 (COVID-19 plasma study): a multicentre study protocol.

Abstract: Since the end of 2019, a new coronavirus strain has been reported in the Chinese province of Wuhan, indicated as 2019-nCoV or SARS-CoV-2. In February 2020, the first case of transmission on Italian soil was reported. On March 09, 2020, at the time of protocol design, the Italian Ministry of Health reported 10,149 people who had contracted the virus; of these, 8514 were positive, of which 5038 were hospitalized with symptoms (59.2%) and 877 in intensive care (10.3%), while the remaining 2599 were in home isolation; 631 were deceased (6.2%) and 1004 healed (9.9%). To date there are no studies in the literature that demonstrate its feasibility and efficacy in the context of the worldwide SARS-CoV-2 epidemic. Based upon the little existing evidence, we planned to assess the efficacy of the infusion of hyperimmune plasma in COVID-19 patients in a one-arm proof-of-concept clinical trial. The primary objective of our study is to evaluate the efficacy of the administration of plasma taken from convalescent donors of COVID-19 to critically ill patients with COVID-19 in terms of their survival. Death from any cause will be considered. The main limit of this study is its one-arm proof-of-concept design with only 43 patients enrolled. However, in the absence of previous evidence, larger and/or randomized trials did not appear to be ethically acceptable. Moreover, the results from this study, if encouraging, will allow us to plan further informed large clinical trials. Trial registration: NCT04321421 March 23, 2020.

Incidence and determinants of high-sensitivity troponin and natriuretic peptides elevation at admission in hospitalized COVID-19 pneumonia patients.

Abstract: Myocardial involvement in the course of coronavirus disease 2019 (COVID-19) pneumonia has been reported, though not fully characterized yet. The aim of the present study is to undertake a joint evaluation of hs-Troponin and natriuretic peptides (NP) in patients hospitalized for COVID-19 pneumonia. In this multicenter observational study, we analyzed data from n = 111 patients. Cardiac biomarkers subgroups were identified according to values beyond reference range. Increased hs-Troponin and NP were found in 38 and 56% of the cases, respectively. As compared to those with normal cardiac biomarkers, these patients were older, had higher prevalence of cardiovascular diseases (CVD) and had more severe COVID-19 pneumonia by higher CRP and d-dimer and lower PaO2/FIO2. Two-dimensional echocardiography performed in a subset of patients (n = 24) showed significantly reduced left ventricular ejection fraction in patients with elevated NP (p = 0.02), whereas right ventricular systolic function (tricuspid annular plane systolic excursion) was significantly reduced both in patients with high hs-Troponin and NP (p = 0.022 and p = 0.03, respectively). Both hs-Troponin and NP were higher in patients with in-hospital mortality (p = 0.001 and p = 0.002, respectively). On multivariable analysis, independent associations were found of hs-Troponin with age, PaO2/FIO2 and d-dimer (B = 0.419, p = 0.001; B = − 0.212, p = 0.013; and B = 0.179, p = 0.037, respectively) and of NP with age and previous CVD (B = 0.480, p < 0.001; and B = 0.253, p = 0.001, respectively). Myocardial involvement at admission is common in COVID-19 pneumonia. Independent associations of hs-Troponin with markers of disease severity and of NP with underlying CVD might point toward existing different mechanisms leading to their elevation in this setting.

Acute headache management in emergency department. A narrative review

Abstract: Headache is a significant reason for access to Emergency Departments (ED) worldwide. Though primary forms represent the vast majority, the life-threatening potential of secondary forms, such as subarachnoid hemorrage or meningitis, makes it imperative for the ED physician to rule out secondary headaches as first step, based on clinical history, careful physical (especially neurological) examination and, if appropriate, hematochemical analyses, neuroimaging or lumbar puncture. Once secondary forms are excluded, distinction among primary forms should be performed, based on the international headache classification criteria. Most frequent primary forms motivating ED observation are acute migraine attacks, particularly status migrainous, and cluster headache. Though universally accepted guidelines do not exist for headache management in an emergency setting, pharmacological parenteral treatment remains the principal approach worldwide, with NSAIDs, neuroleptic antinauseants, triptans and corticosteroids, tailored to the specific headache type. Opioids should be avoided, for their scarce effectiveness in the acute phase, while IV hydration should be limited in cases of ascertained dehydration. Referral of the patient to a Headache Center should subsequently be an integral part of the ED approach to the headache patients, being ascertained that lack of this referral involves a high rate of relapse and new accesses to the ED. More controlled studies are needed to establish specific protocols of management for the headache patient in the ED.

Anaemia, iron homeostasis and pulmonary hypertension: a review

Abstract: Anaemia is a highly prevalent condition, which negatively impacts on patients’ cardiovascular performance and quality of life. Anaemia is mainly caused by disturbances of iron homeostasis. While absolute iron deficiency mostly as a consequence of chronic blood loss or insufficient dietary iron absorption results in the emergence of iron deficiency anaemia, inflammation-driven iron retention in innate immune cells and blockade of iron absorption leads to the development of anaemia of chronic disease. Both, iron deficiency and anaemia have been linked to the clinical course of pulmonary hypertension. Various mechanistic links between iron homeostasis, anaemia, and pulmonary hypertension have been described and current treatment guidelines suggest regular iron status assessment and the implementation of iron supplementation strategies in these patients. The pathophysiology, diagnostic assessment as well as current and future treatment options concerning iron deficiency with or without anaemia in individuals suffering from pulmonary hypertension are discussed within this review.

Flowchart for non-invasive ventilation support in COVID-19 patients from a northern Italy Emergency Department.

Abstract: With the rapid pandemic spread of the novel coronavirus (SARS-CoV2), Emergency Departments of affected countries are facing an increasing number of patients presenting with hypoxemic respiratory failure due to coronavirus disease 2019 (COVID-19). Providing mechanical support and endotracheal intubation can be challenging due to a number of patients larger than usual, often exceeding available resources. Considering the lack of recommendations available, we developed a flowchart to standardize the first approach to patients presenting to the Emergency Department with hypoxemic respiratory failure due to COVID-19.

Impact of COVID-19 on liver function: results from an internal medicine unit in Northern Italy.

Abstract: Little is known regarding coronavirus disease 2019 (COVID-19) clinical spectrum in non-Asian populations. We herein describe the impact of COVID-19 on liver function in 100 COVID-19 consecutive patients (median age 70 years, range 25–97; 79 males) who were admitted to our internal medicine unit in March 2020. We retrospectively assessed liver function tests, taking into account demographic characteristics and clinical outcome. A patient was considered as having liver injury when alanine aminotransferase (ALT) was > 50 mU/ml, gamma-glutamyl transpeptidase (GGT) > 50 mU/ml, or total bilirubin > 1.1 mg/dl. Spearman correlation coefficient for laboratory data and bivariable analysis for mortality and/or need for intensive care were assessed. A minority of patients (18.6%) were obese, and most patients were non- or moderate-drinkers (88.5%). Liver function tests were altered in 62.4% of patients, and improved during follow-up. None of the seven patients with known chronic liver disease had liver decompensation. Only one patient developed acute liver failure. In patients with altered liver function tests, PaO2/FiO2 < 200 was associated with greater mortality and need for intensive care (HR 2.34, 95% CI 1.07–5.11, p = 0.033). To conclude, a high prevalence of altered liver function tests was noticed in Italian patients with COVID-19, and this was associated with worse outcomes when developing severe acute respiratory distress syndrome.

COVID-19: counter-intuitive data on smoking prevalence and therapeutic implications for nicotine.

Abstract: All the world is aware of the Coronavirus pandemic, and as of the 23rd of April 2020 globally 2.629.801 cases had been confirmed, and 183.454 fatalities had occurred (https ://coron aviru s.jhu.edu/map.html). The world is struggling and working to contain the disease and death of this active new virus. On top of the medical toll, the COVID-19 pandemic has resulted in severe economic devastation that has tragic and widespread consequences for human health and suffering. Multiple strategies are necessary to end this pandemic. Some of these actions are supplying all health professionals with personal protective equipment, reorganizing healthcare systems with COVID-19 dedicated high-dependency hospitals/wards, testing new treatments and vaccines, and motivating people to maintain social distancing practices even when the pandemic recedes. In the absence of long-term immunization against SARSCoV-2 or effective therapies for COVID-19, healthcare professionals must have access to clear information that accurately predicts which patients with the virus would go on to develop clinical deterioration of COVID-19 (high-risk populations). A better clinical definition of those at highrisk for severe illness with COVID-19 is vital for effective clinical assessment, risk stratification, resource allocation repositioning, and targeted public health interventions. Some conclusive predictors of the risks for severe illness have been clearly described: the presence of co-morbidities [1], older age [2], breathlessness [3] and lymphopenia [4]. Many other predictors of COVID-19 that result in clinical severity have been proposed, but their validity has been questioned. The difficulty in identifying predictors is not surprising considering that anamnestic and behavioral data might have been collected inaccurately due to the extremely challenging situations at wards/ICUs with work overloads and operating in a persistent state of emergency. Intuitively, one vulnerability to severe illness from COVID-19 would be assumed to be cigarette smoking [8] because it is known to increase the risk of serious respiratory infections [5–7]. But is this in fact true? In this issue of Internal and Emergency Medicine, Farsalinos et al. [9] explore the hypothesis that smokers are at higher risk and unexpectedly found data that point to the opposite and counter-intuitive conclusion that smoking may actually have a protective effect. Their systematic review observed that smoking is vastly protective for hospitalized COVID19 based on the surprisingly low prevalence of smoking in patients hospitalized with COVID-19. While it is possible that the prevalence of smokers in Chinese case series may be underrepresented due to inaccurate recording of their smoking status, similar findings have been now being reported in the US, Germany and in France. The Centers for Disease Control and Prevention (CDC) [10] report an unusually low prevalence of current smoking among COVID-19 cases at 1.3% compared to population smoking prevalence in US of 16.5% [11]. A cross-sectional analysis of 4103 laboratoryconfirmed COVID-19 patients treated at academic hospitals in New York City, demonstrated again a low smoking prevalence of 5.2% [12]. A multivariate analysis performed by the New York researchers showed a significant protective effect against hospitalization among current and former tobacco users (OR = 0.71, 95% CI 0.57–0.87 p = 0.001). Moreover, smoking was not a risk factor for critical disease or death. In Germany, a recent case series of hospitalized COVID-19 patients found a low smoking prevalence of about 6% [13]. The protective association has been also recently observed in France where smoking prevalence reported for various age groups and levels of disease severity roughly average to about 1/5 of the population prevalence [14]. These findings * Riccardo Polosa polosa@unict.it

Prediction of general medical admission length of stay with natural language processing and deep learning: a pilot study

Abstract: Length of stay (LOS) and discharge destination predictions are key parts of the discharge planning process for general medical hospital inpatients. It is possible that machine learning, using natural language processing, may be able to assist with accurate LOS and discharge destination prediction for this patient group. Emergency department triage and doctor notes were retrospectively collected on consecutive general medical and acute medical unit admissions to a single tertiary hospital from a 2-month period in 2019. These data were used to assess the feasibility of predicting LOS and discharge destination using natural language processing and a variety of machine learning models. 313 patients were included in the study. The artificial neural network achieved the highest accuracy on the primary outcome of predicting whether a patient would remain in hospital for > 2 days (accuracy 0.82, area under the received operator curve 0.75, sensitivity 0.47 and specificity 0.97). When predicting LOS as an exact number of days, the artificial neural network achieved a mean absolute error of 2.9 and a mean squared error of 16.8 on the test set. For the prediction of home as a discharge destination (vs any non-home alternative), all models performed similarly with an accuracy of approximately 0.74. This study supports the feasibility of using natural language processing to predict general medical inpatient LOS and discharge destination. Further research is indicated with larger, more detailed, datasets from multiple centres to optimise and examine the accuracy that may be achieved with such predictions.

Cardiac involvement at presentation in patients hospitalized with COVID-19 and their outcome in a tertiary referral hospital in Northern Italy.

Abstract: The correlation between myocardial injury and clinical outcome in COVID-19 patients is gaining attention in the literature. The aim of the present study was to evaluate the role of cardiac involvement and of respiratory failure in a cohort of COVID-19 patients hospitalized in an academic hospital in Lombardy, one of the most affected Italian (and worldwide) regions by the epidemic. The study included 405 consecutive patients with confirmed COVID-19 admitted to a medical ward from February 25th to March 31st, 2020. Follow-up of surviving patients ended either at hospital discharge or by July 30th, 2020. Myocardial injury was defined on the basis of the presence of blood levels of hs-TnI above the 99th percentile upper reference limit. Respiratory function was assessed as PaO2/FiO2 (P/F) ratio. The primary end-point was death for any cause. During hospitalization, 124 patients died. Death rate increased from 7.9% in patients with normal hs-TnI plasma levels and no cardiac comorbidity to 61.5% in patients with elevated hs-TnI and cardiac involvement (p < 0.001). At multivariable analysis, older age, P/F ratio < 200 (both p < 0.001) and hs-TnI plasma levels were independent predictors of death. However, it must be emphasized that the median values of hs-TnI were within normal range in non-survivors. Cardiac involvement at presentation was associated with poor prognosis in COVID-19 patients, but, even in a population of COVID-19 patients who did not require invasive ventilation at hospital admission, mortality was mainly driven by older age and respiratory failure.