Showing papers in "Internal and Emergency Medicine in 2021"

Deep vein thrombosis (DVT) occurring shortly after the second dose of mRNA SARS-CoV-2 vaccine.

Abstract: Currently, the SARS-CoV-19 pandemic represents the leading global health emergency, and vaccines are the primary health strategy to eradicate this global challenge. In Europe, three vaccines have been approved by the European Medicines Agency (EMA), two based on mRNA technology, and one with an adenovirus vector [1]. Published data show high protective efficacy rates in the face of mostly mild-tomoderate and short-lasting adverse effects, mainly after the second dose [2–4]. Venous thromboembolic (VTE) complications have been consistently reported to be increased in SARS-CoV-2 infection, most probably as the results of a thrombophilic state secondary to inflammation and immunethrombosis [5]. On the other hand, no reports are available regarding a possible association between VTE and SARSCov-2 post-vaccine acute-phase reaction. Here we describe a case of distal deep vein thrombosis occurring immediately days after the second dose of mRNA vaccine. A 66-year-old woman received the first dose of mRNA Covid-19 vaccine (BNT162b2, Comirnaty, Pfizer/BioNTech) subcutaneously on January 4th, 2021, without any reported clinical problem; she was scheduled for the second dose on January 25th. Her medical history was unremarkable except for post-trauma left leg neuropathy. She never had previous thrombotic events; she had one successful delivery. Her body mass index was 23 kg/m2; she did not smoke or had no allergic problems; she intermittently took painkillers for the neuropathy. On January 26th, 24 h after the second vaccine dose, she received acetaminophen for persistent fever with chills, fatigue, malaise, and muscle pain. On January 27th, 48 h after the second vaccine dose, persistent fever was still present, and acute right calf pain appeared in the absence of trauma. On January 28th, she was admitted for evaluation at the emergency room because of persistent pain and inability to walk. Physical examination was unremarkable except for mild edema in the right calf. Blood tests (Blood count, INR, PTT, fibrinogen, renal and hepatic function) were normal, as notably was the D-dimer measurement. A Color-Doppler ultrasound scan revealed the presence of deep vein thrombosis involving the right peroneal vein and extending up to the popliteal vein, without signs of venous insufficiency. Thrombophilia screening was otherwise negative except for the presence of heterozygous FV Leiden mutation. The patient started apixaban 10 mg bid for 1 week, followed by 5 mg bid, with rapid symptoms resolution. To our knowledge, this is the first reported case of DVT presenting as an adverse event post-SARS-CoV-2 vaccination. Arguably, the intense immunological response evoked by the second dose of vaccine could be a trigger for the thrombotic event described, a mechanism recognized in many clinical conditions. No DVT cases have been reported on 21,720 persons receiving BNT162b2, suggesting that the DVT incidence may be lower than one case every 5889 (this figure representing the 95% upper boundary of confidence interval) [4]. No apparent correlation can be made with the presence of a mild thrombophilia mutation in this patient. In our district, the vaccination program started on January 2021 and involved only health workers, of whom 3010 received two doses on January 25th. This case notwithstanding, we may consider that DVT post-vaccination incidence may still be very low and within the expected incidence figure. A longer follow-up and a greater diffusion of SARS-CoV-2 vaccines in the population are needed * Alberto Tosetto alberto.tosetto@aulss8.veneto.it

Myocarditis in COVID-19 patients: current problems.

Abstract: Myocarditis has been reported as a possible clinical presentation or complication in patients with coronavirus disease (COVID)-19 due to SARS-CoV-2. Despite the alarm that this possibility generated among physicians, there is paucity of information about mechanisms, prevalence, prognosis, diagnosis and therapy of myocarditis in the context of COVID-19. This brief review has the goal to revise and summarize current knowledge on myocarditis in COVID-19 patients and underline problems especially related to diagnosis and treatment.

Disorders of sodium balance and its clinical implications in COVID-19 patients: a multicenter retrospective study.

Abstract: The worldwide spread of SARS-CoV-2 has infected millions of people leading to over 0.3 million mortalities. The disruption of sodium homeostasis, tends to be a common occurrence in patients with COVID-19. A total of 1,254 COVID-19 patients comprising 124 (9.9%) hyponatremic patients (under 135 mmol/L) and 30 (2.4%) hypernatremic patients (over 145 mmol/L) from three hospitals in Hubei, China, were enrolled in the study. The relationships between sodium balance disorders in COVID-19 patients, its clinical features, implications, and the underlying causes were presented. Hyponatremia patients were observed to be elderly, had more comorbidities, with severe pneumonic chest radiographic findings. They were also more likely to have a fever, nausea, higher leukocyte and neutrophils count, and a high sensitivity C-reactive protein (HS-CRP). Compared to normonatremia patients, renal insufficiency was common in both hyponatremia and hypernatremia patients. In addition, hyponatremia patients required extensive treatment with oxygen, antibiotics, and corticosteroids. The only significant differences between the hypernatremia and normonatremia patients were laboratory findings and clinical complications, and patients with hypernatremia were more likely to use traditional Chinese medicine for treatment compared to normonatremia patients. This study indicates that severity of the disease, the length of stay in the hospital of surviving patients, and mortality were higher among COVID-19 patients with sodium balance disorders. Sodium balance disorder, particularly hyponatremia, is a common condition among hospitalized patients with COVID-19 in Hubei, China, and it is associated with a higher risk of severe illness and increased in-hospital mortality.

COVID-19 coagulopathy: is it disseminated intravascular coagulation?

Abstract: One of the significant complications of severe COVID-19 infections is a coagulopathy that seems to be related to the occurrence of venous and arterial thromboembolic disease. The coagulation changes mimic but are not identical to disseminated intravascular coagulation (DIC). The vast majority of patients with COVID-19 do not meet the criteria for usual forms of DIC. In addition, there seem to be features of a strong local pulmonary thrombotic microangiopathy and direct endothelial cell infection and injury by the virus that affect the coagulopathic response to severe COVID-19. It seems COVID-19 leads to a distinct intravascular coagulation syndrome that may need separate diagnostic criteria.

TMAO as a biomarker of cardiovascular events: a systematic review and meta-analysis

Abstract: Unmasking the residual cardiovascular risk is a major research challenge in the attempt to reduce cardiovascular disease (CVD) morbidity and mortality. Mounting evidence suggests that a high circulating level of trimethylamine N-oxide is a new potential CVD risk factor. We performed a systematic review of the published studies to clarify the association between circulating high levels of TMAO and cardiovascular events. Studies evaluating the association between TMAO and CVD events were searched by electronic databases up to December 2018. Pooled results were expressed as risk ratio (RR) with 95% pertinent confidence interval (CI). Three studies for a total of 923 patients at high/very high CVD risk were included in our analysis. Overall, a high TMAO level was associated with both major adverse cardiovascular events (RR = 2.05; 95% CI 1.61–2.61) and all-cause mortality (RR = 3.42; 95% CI 2.27–5.15). Our findings support a role of high TMAO levels in predicting CVD events. High levels of TMAO may be a new CVD risk factor, potentially useful to better plan personalized CVD prevention strategies.

A narrative review of coronavirus disease 2019 (COVID-19): clinical, epidemiological characteristics, and systemic manifestations.

Abstract: Coronavirus disease 2019 (COVID-19) is an emerging infectious disease which has had a rapid surge in cases and deaths since it is first documented in Wuhan, China, in December 2019. COVID-19 is caused by the Betacoronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 uses angiotensin-converting enzyme 2, which is highly expressed in the human lower respiratory tract but also in other tissues, as the cellular entry receptor. Thus, COVID-19 mainly affects the respiratory system but can cause damage to other body systems, including the cardiovascular, gastrointestinal, hepatobiliary, renal, and central nervous systems. We review the pathogenesis and clinical manifestations of the infection, focusing on our current understanding of the disease mechanisms and their translation to clinical outcomes, as well as adverse effects on different body systems. We also discuss the epidemiology pathogenesis, clinical, and multi-organ consequences, and highlight some of the research gaps regarding COVID-19.

A randomized clinical trial evaluating the immunomodulatory effect of convalescent plasma on COVID-19-related cytokine storm.

Abstract: Evaluating the effect of convalescent plasma (CP) on some cytokine storm indices in severe COVID-19 patients. Totally, 62 patients were randomly assigned into two groups for this clinical trial. Patients in the intervention group received one unit (500 mL) plasma on the admission day plus standard drugs while the controls merely received standard treatments. Eventually, primary and secondary outcomes were evaluated. In the CP group, compared with controls, the mean levels of lymphocytes and IL-10 significantly increased while the levels of IL-6, TNF-α, and IFN-γ decreased (p 0.05) while WHO severity scores remarkably improved (p = 0.01), despite the higher frequency of underlying diseases among the CP group (66.7%) vs. controls (33.3%). Although CP has a remarkable immunomodulatory and antiviral potential to improve the cytokine storm and disease severity in COVID-19 patients, it did not considerably affect the mortality rate.

Predictors of mortality of COVID-19 in the general population and nursing homes.

Abstract: The factors that predispose an individual to a higher risk of death from COVID-19 are poorly understood. The goal of the study was to identify factors associated with risk of death among patients with COVID-19. This is a retrospective cohort study of people with laboratory-confirmed SARS-CoV-2 infection from February to May 22, 2020. Data retrieved for this study included patient sociodemographic data, baseline comorbidities, baseline treatments, other background data on care provided in hospital or primary care settings, and vital status. Main outcome was deaths until June 29, 2020. In the multivariable model based on nursing home residents, predictors of mortality were being male, older than 80 years, admitted to a hospital for COVID-19, and having cardiovascular disease, kidney disease or dementia while taking anticoagulants or lipid-lowering drugs at baseline was protective. The AUC was 0.754 for the risk score based on this model and 0.717 in the validation subsample. Predictors of death among people from the general population were being male and/or older than 60 years, having been hospitalized in the month before admission for COVID-19, being admitted to a hospital for COVID-19, having cardiovascular disease, dementia, respiratory disease, liver disease, diabetes with organ damage, or cancer while being on anticoagulants was protective. The AUC was 0.941 for this model's risk score and 0.938 in the validation subsample. Our risk scores could help physicians identify high-risk groups and establish preventive measures and better follow-up for patients at high risk of dying.ClinicalTrials.gov Identifier: NCT04463706.

Clinical characteristics and respiratory support of 310 COVID-19 patients, diagnosed at the emergency room: a single-center retrospective study.

Abstract: An ongoing outbreak of pneumonia associated with severe acute respiratory coronavirus 2 (SARS-CoV-2) occurred at the end of February 2020 in Lombardy, Italy. We analyzed data from a retrospective, single-center case series of 310 consecutive patients, with confirmed SARS-CoV-2 infection, admitted to the emergency room. We aimed to describe the clinical course, treatment and outcome of a cohort of patients with COVID-19 pneumonia, with special attention to oxygen delivery and ventilator support. Throughout the study period, 310 consecutive patients, with confirmed SARS-CoV-2 infection, attended the Emergency Room (ER), of these, 34 were discharged home directly from the ER. Of the remaining 276 patients, the overall mortality was 30.4%: 7 patients died in the ER and 77 during hospitalization. With respect to oxygen delivery: 22 patients did not need any oxygen support (8.0%), 151 patients were treated with oxygen only (54.7%), and 49 (17.8%) were intubated. 90 patients (32.6%) were treated with CPAP (Continuous Positive Airway Pressure) or NIV (Non Invasive Ventilation); in this group, 27 patients had a Do Not Intubate (DNI) order and were treated with CPAP/NIV as an upper threshold therapy, showing high mortality rate (88.9%). Among the 63 patients treated with CPAP/NIV without DNI, NIV failure occurred in 36 patients (57.1%), with mortality rate of 47.2%. Twenty-seven (27) patients were treated with CPAP/NIV without needing mechanical ventilation and 26 were discharged alive (96.3%). The study documents the poor prognosis of patients with severe respiratory failure, although a considerable minority of patients treated with CPAP/NIV had a positive outcome.

COVID-19 treatment options: a difficult journey between failed attempts and experimental drugs.

Abstract: Since its outbreak in China in December 2019 a novel Coronavirus, named SARS-CoV-2, has spread worldwide causing many cases of severe pneumonia, referred to as COVID-19 disease, leading the World Health Organization to declare a pandemic emergency in March 2020. Up to now, no specific therapy against COVID-19 disease exists. This paper aims to review COVID-19 treatment options currently under investigation. We divided the studied drugs into three categories (antiviral, immunomodulatory and other drugs). For each molecule, we discussed the putative mechanisms by which the drug may act against SARS-CoV-2 or may affect COVID-19 pathogenesis and the main clinical studies performed so far. The published clinical studies suffer from methodological limitations due to the emergency setting in which they have been conducted. Nevertheless, it seems that the timing of administration of the diverse categories of drugs is crucial in determining clinical efficacy. Antiviral drugs, in particular Remdesivir, should be administered soon after symptoms onset, in the viraemic phase of the disease; whereas, immunomodulatory agents, such as tocilizumab, anakinra and steroids, may have better results if administered in pneumonia/hyperinflammatory phases. Low-molecular-weight heparin may also have a role when facing COVID-19-related coagulopathy. Up to now, treatment choices have been inferred from the experience with other coronaviruses or viral infection outbreaks. Hopefully, in the near future, new treatment strategies will be available thanks to increased knowledge on SARS-CoV2 virus and COVID-19 pathogenesis. In the meanwhile, further well-designed clinical trials are urgently needed to establish a standard of care in COVID-19 disease.

Diagnosis and management of leukocytoclastic vasculitis

Abstract: Leukocytoclastic vasculitis (LCV) is a histopathologic description of a common form of small vessel vasculitis (SVV), that can be found in various types of vasculitis affecting the skin and internal organs. The leading clinical presentation of LCV is palpable purpura and the diagnosis relies on histopathological examination, in which the inflammatory infiltrate is composed of neutrophils with fibrinoid necrosis and disintegration of nuclei into fragments (“leukocytoclasia”). Several medications can cause LCV, as well as infections, or malignancy. Among systemic diseases, the most frequently associated with LCV are ANCA-associated vasculitides, connective tissue diseases, cryoglobulinemic vasculitis, IgA vasculitis (formerly known as Henoch–Schonlein purpura) and hypocomplementemic urticarial vasculitis (HUV). When LCV is suspected, an extensive workout is usually necessary to determine whether the process is skin-limited, or expression of a systemic vasculitis or disease. A comprehensive history and detailed physical examination must be performed; platelet count, renal function and urinalysis, serological tests for hepatitis B and C viruses, autoantibodies (anti-nuclear antibodies and anti-neutrophil cytoplasmic antibodies), complement fractions and IgA staining in biopsy specimens are part of the usual workout of LCV. The treatment is mainly focused on symptom management, based on rest (avoiding standing or walking), low dose corticosteroids, colchicine or different unproven therapies, if skin-limited. When a medication is the cause, the prognosis is favorable and the discontinuation of the culprit drug is usually resolutive. Conversely, when a systemic vasculitis is the cause of LCV, higher doses of corticosteroids or immunosuppressive agents are required, according to the severity of organ involvement and the underlying associated disease.

Lung ultrasound as diagnostic tool for SARS-CoV-2 infection.

Abstract: The aim of this study was to explore the role of lung ultrasound (LUS) in the diagnosis of SARS-CoV-2 infection and to verify its utility in the prediction of lung disease's severity and outcome. Fifty-three consecutive patients presenting to the Emergency Department of Santa Maria delle Grazie Hospital with high suspicion of SARS-CoV-2 infection underwent diagnostic test for SARS-CoV-2 on samples obtained from nasopharyngeal swab as well as complete proper diagnostic work-up that included clinical evaluation, laboratory tests, blood gas analyses, chest CT and LUS. A semiquantitative analysis of B-lines distribution was performed to calculate the LUS score. Patients were divided into two groups according to the results of both SARS-CoV-2 diagnostic test and other exams (Group A = pneumonia due to SARS-CoV2 infection vs Group B = no SARS-CoV2 infection and another definite diagnosis). LUS showed an excellent accuracy in predicting the diagnosis of SARS-CoV-2 infection (area under the ROC curve of 0.92 with a sensibility of 73% and a specificity of 89% a the cut-off of 12.5). LUS score was more impaired in SARS-CoV-2 patients (18.1 ± 6.0 vs 7.6 ± 5.9, p < 0.00001) and it is significantly negatively correlated with PF ratio values (r = - 0.719, p < 0.0001). An intrahospital mortality rate of 46% was found; patients with adverse outcome had significant higher value of LUS, PF, LDH, and APACHE II score. None of these parameters was predictive of mortality. LUS is a useful tool for the early detection of SARS-CoV-2 infection and for the evaluation of the disease severity, but does not predict mortality. Further studies with repeated evaluations of LUS score are needed to further explore the role of LUS in the assessment of severity in SARS-CoV-2 disease and in the monitoring of the response to treatments.

Effect of influenza vaccine on COVID-19 mortality: a retrospective study.

Abstract: It has been proposed that vaccines may exert an unspecific protective effect against infectious agents, different than expected. Coronavirus disease 2019 (COVID-19) is a pandemic infection with high mortality in older patients due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The high number of vaccinations may be one of the reasons why children show a lower susceptibility to SARS-CoV-2 infection and milder severity when compared to adults. We have designed a study aimed at investigating whether the influenza vaccine may reduce the susceptibility and severity of SARS-CoV-2 infection. We retrospectively enrolled 635 patients who accessed our Emergency Department from March 1st to June 30th, 2020, and were diagnosed with COVID-19 infection confirmed by an RT-PCR on an oropharyngeal swab. Clinical data, outcomes, and influenza vaccination status were collected from the electronic medical records of our Hospital. We also used data from the Italian Health Ministry to compare the prevalence of flu vaccination among the general population of the Lazio Region and our enrolled patients. We then compared clinical outcomes between vaccinated and non-vaccinated patients, by univariate and multivariate analysis. COVID-19-positive patients older than 65 years reported a lower prevalence of flu vaccination when compared to the general population residing in the Lazio (p = 0.004). After correction for gender, age, and comorbidities, we found a lower risk of death at 60 days in patients with flu vaccination than in not vaccinated patients (p = 0.001). Our study shows that flu vaccination could reduce the mortality of COVID-19. Prospective studies are needed to confirm this result.

The role of lung ultrasound as a frontline diagnostic tool in the era of COVID-19 outbreak.

Abstract: The diffusion of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) worldwide prompted the World Health Organization to declare the status of pandemic. The molecular diagnosis of SARS-CoV-2 infection is based on the detection of viral RNA on different biological specimens. Unfortunately, the test may require several hours to be performed. In the present study, we evaluated the diagnostic accuracy of lung point-of-care ultrasound (POCUS) for SARS-CoV-2 pneumonia in a cohort of symptomatic patients admitted to one emergency department (ED) in a high-prevalence setting. This retrospective study enrolled all patients who visited one ED with suspected respiratory infection in March 2020. All the patients were tested (usually twice if the first was negative) for SARS-CoV-2 on ED admission. The reference standard was considered positive if at least one specimen was positive. If all the specimens tested negative, the reference was considered negative. Diagnostic accuracy was evaluated using sensitivity, specificity, and positive and negative predictive value. Of the 444 symptomatic patients who were admitted to the ED in the study period, the result of the lung POCUS test was available for 384 (86.5%). The sensitivity of the test was 92.0% (95% CI 88.2-94.9%), and the specificity was 64.9% (95% CI 54.6-74.4%). We observed a prevalence of SARS-CoV-2 infection of 74.7%. In this setting, the positive and negative predicted values were 88.6% (95% CI 84.4-92.0) and 73.3% (95% CI 62.6-82.2%), respectively. Lung POCUS is a sensitive first-line screening tool for ED patients presenting with symptoms suggestive of SARS-CoV-2 infection.

Electrolyte imbalance in COVID-19 patients admitted to the Emergency Department: a case-control study.

Abstract: In patients visiting the emergency department (ED), a potential association between electrolytes disturbance and coronavirus disease 2019 (COVID-19) has not been well studied. We aim to describe electrolyte disturbance and explore risk factors for COVID-19 infection in patients visiting the ED. We carried out a case–control study in three hospitals in France, including adult ED inpatients (≥ 18 years old). A total of 594 ED case patients in whom infection with COVID-19 was confirmed, were matched to 594 non-COVID-19 ED patients (controls) from the same period, according to sex and age. Hyponatremia was defined by a sodium of less than 135 mmol/L (reference range 135–145 mmol/L), hypokalemia by a potassium of less than 3.5 mmol/L (reference range 3.5–5.0 mmol/L), and hypochloremia by a chloride of less than 95 mmol/L (reference range 98–108 mmol/L). Among both case patients and controls, the median (IQR) age was 65 years (IQR 51–76), and 44% were women. Hyponatremia was more common among case patients than among controls, as was hypokalemia and hypochloremia. Based on the results of the multivariate logistic regression, hyponatremia, and hypokalemia were associated with COVID-19 among case patients overall, with an adjusted odds ratio of 1.89 [95% CI 1.24–2.89] for hyponatremia and 1.76 [95% CI 1.20–2.60] for hypokalemia. Hyponatremia and hypokalemia are independently associated with COVID-19 infection in adults visiting the ED, and could act as surrogate biomarkers for the emergency physician in suspected COVID-19 patients.

Diagnosis and management of acute aortic syndromes in the emergency department

Abstract: Acute aortic syndromes (AASs) are deadly cardiovascular emergencies involving the thoracic aorta. AASs are relatively rare conditions, have unspecific signs and symptoms (including truncal pain, syncope, neurologic deficit and limb ischemia) and require contrast-enhanced tomography angiography (CTA) of the chest and abdomen for conclusive diagnosis and subsequent therapeutic planning. In the Emergency Department (ED), most patients with potential signs/symptoms of AASs are finally found affected by other alternative diagnoses. Hence, misdiagnosis and delayed diagnosis of AASs are major concerns. In critically ill patients, decision to perform CTA is usually straightforward, as exam benefits largely outweigh risks. In patients with ST-tract elevation on ECG, suspected primary ischemic stroke and in stable patients (representing the most prevalent ED scenarios), proper selection of patients necessitating CTA is cumbersome, due to concurrent risks of misdiagnosis and over-testing. Available studies support an algorithm integrating clinical probability assessment, bedside echocardiography and d-dimer (if the clinical probability is not high). Therapeutic management includes medical therapy for all patients including an opioid and anti-impulse drugs (a beta-blocker and a vasodilator), targeting a heart rate of 60 bpm and systolic blood pressure of 100–120 mmHg. Patients with AASs involving the ascending aorta are likely candidate for urgent surgery, and complicated type B AASs (severe aortic dilatation, impending or frank rupture, organ malperfusion, refractory pain, severe hypertension) necessitate evaluation for urgent endovascular treatment. For uncomplicated type B AASs, optimal medical therapy is the current standard of care.

Cardiac injury and mortality in patients with Coronavirus disease 2019 (COVID-19): insights from a mediation analysis.

Abstract: Patients at greatest risk of severe clinical conditions from coronavirus disease 2019 (COVID-19) and death are elderly and comorbid patients. Increased levels of cardiac troponins identify patients with poor outcome. The present study aimed to describe the clinical characteristics and outcomes of a cohort of Italian inpatients, admitted to a medical COVID-19 Unit, and to investigate the relative role of cardiac injury on in-hospital mortality. We analyzed all consecutive patients with laboratory-confirmed COVID-19 referred to our dedicated medical Unit between February 26th and March 31st 2020. Patients’ clinical data including comorbidities, laboratory values, and outcomes were collected. Predictors of in-hospital mortality were investigated. A mediation analysis was performed to identify the potential mediators in the relationship between cardiac injury and mortality. A total of 109 COVID-19 inpatients (female 36%, median age 71 years) were included. During in-hospital stay, 20 patients (18%) died and, compared with survivors, these patients were older, had more comorbidities defined by Charlson comorbidity index ≥ 3(65% vs 24%, p = 0.001), and higher levels of high-sensitivity cardiac troponin I (Hs-cTnI), both at first evaluation and peak levels. A dose–response curve between Hs-cTnI and in-hospital mortality risk up to 200 ng/L was detected. Hs-cTnI, chronic kidney disease, and chronic coronary artery disease mediated most of the risk of in-hospital death, with Hs-cTnI mediating 25% of such effect. Smaller effects were observed for age, lactic dehydrogenase, and d-dimer. In this cohort of elderly and comorbid COVID-19 patients, elevated Hs-cTnI levels were the most important and independent mediators of in-hospital mortality.

Mortality risk assessment in Spain and Italy, insights of the HOPE COVID-19 registry.

Abstract: Recently the coronavirus disease (COVID-19) outbreak has been declared a pandemic. Despite its aggressive extension and significant morbidity and mortality, risk factors are poorly characterized outside China. We designed a registry, HOPE COVID-19 (NCT04334291), assessing data of 1021 patients discharged (dead or alive) after COVID-19, from 23 hospitals in 4 countries, between 8 February and 1 April. The primary end-point was all-cause mortality aiming to produce a mortality risk score calculator. The median age was 68 years (IQR 52–79), and 59.5% were male. Most frequent comorbidities were hypertension (46.8%) and dyslipidemia (35.8%). A relevant heart or lung disease were depicted in 20%. And renal, neurological, or oncological disease, respectively, were detected in nearly 10%. Most common symptoms were fever, cough, and dyspnea at admission. 311 patients died and 710 were discharged alive. In the death-multivariate analysis, raised as most relevant: age, hypertension, obesity, renal insufficiency, any immunosuppressive disease, 02 saturation 0.999; bootstrap-optimist: 0.0018). We provide a simple clinical score to estimate probability of death, dividing patients in four grades (I–IV) of increasing probability. Hydroxychloroquine (79.2%) and antivirals (67.6%) were the specific drugs most commonly used. After a propensity score adjustment, the results suggested a slight improvement in mortality rates (adjusted-ORhydroxychloroquine 0.88; 95% CI 0.81–0.91, p = 0.005; adjusted-ORantiviral 0.94; 95% CI 0.87–1.01; p = 0.115). COVID-19 produces important mortality, mostly in patients with comorbidities with respiratory symptoms. Hydroxychloroquine could be associated with survival benefit, but this data need to be confirmed with further trials. Trial Registration: NCT04334291/EUPAS34399.

Clinical factors associated with death in 3044 COVID-19 patients managed in internal medicine wards in Italy: results from the SIMI-COVID-19 study of the Italian Society of Internal Medicine (SIMI).

Abstract: During the COVID-19 2020 outbreak, a large body of data has been provided on general management and outcomes of hospitalized COVID-19 patients. Yet, relatively little is known on characteristics and outcome of patients managed in Internal Medicine Units (IMU). To address this gap, the Italian Society of Internal Medicine has conducted a nationwide cohort multicentre study on death outcome in adult COVID-19 patients admitted and managed in IMU. This study assessed 3044 COVID-19 patients at 41 referral hospitals across Italy from February 3rd to May 8th 2020. Demographics, comorbidities, organ dysfunction, treatment, and outcomes including death were assessed. During the study period, 697 patients (22.9%) were transferred to intensive care units, and 351 died in IMU (death rate 14.9%). At admission, factors independently associated with in-hospital mortality were age (OR 2.46, p = 0.000), productive cough (OR 2.04, p = 0.000), pre-existing chronic heart failure (OR 1.58, p = 0.017) and chronic obstructive pulmonary disease (OR 1.17, p = 0.048), the number of comorbidities (OR 1.34, p = 0.000) and polypharmacy (OR 1.20, p = 0.000). Of note, up to 40% of elderly patients did not report fever at admission. Decreasing PaO2/FiO2 ratio at admission was strongly inversely associated with survival. The use of conventional oxygen supplementation increased with the number of pre-existing comorbidities, but it did not associate with better survival in patients with PaO2/FiO2 ratio < 100. The latter, significantly benefited by the early use of non-invasive mechanical ventilation. Our study identified PaO2/FiO2 ratio at admission and comorbidity as the main alert signs to inform clinical decisions and resource allocation in non-critically ill COVID-19 patients admitted to IMU.

Serial KL-6 measurements in COVID-19 patients.

Abstract: SARS-CoV2-induced direct cytopathic effects against type II pneumocytes are suspected to play a role in mediating and perpetuating lung damage. The aim of this study was to evaluate serum KL-6 behavior in COVID-19 patients to investigate its potential role in predicting clinical course. Sixty patients (median age IQR, 65 (52-69), 43 males), hospitalized for COVID-19 at Siena COVID Unit University Hospital, were prospectively enrolled. Twenty-six patients were selected (median age IQR, 63 (55-71), 16 males); all of them underwent follow-up evaluations, including clinical, radiological, functional, and serum KL-6 assessments, after 6 (t1) and 9 (t2) months from hospital discharge. At t0, KL-6 concentrations were significantly higher than those at t1 (760 (311-1218) vs. 309 (210-408) p = 0.0208) and t2 (760 (311-1218) vs 324 (279-458), p = 0.0365). At t0, KL-6 concentrations were increased in patients with fibrotic lung alterations than in non-fibrotic group (755 (370-1023) vs. 305 (225-608), p = 0.0225). Area under the receiver operating curve (AUROC) analysis showed that basal KL-6 levels showed good accuracy in discriminating patients with fibrotic sequelae radiologically documented (AUC 85%, p = 0.0404). KL-6 concentrations in patients with fibrotic involvement were significantly reduced at t1 (755 (370-1023) vs. 290 (197-521), p = 0.0366) and t2 (755 (370-1023) vs. 318 (173-435), p = 0.0490). Serum concentrations of KL-6 in hospitalized COVID-19 patients may contribute to identify severe patients requiring mechanical ventilation and to predict those who will develop pulmonary fibrotic sequelae in the follow-up.

Increasing dosages of low-molecular-weight heparin in hospitalized patients with Covid-19.

Abstract: We conducted an observational cohort study in adult patients consecutively admitted for the respiratory illness Covid-19 to our hub hospital from March 9 to April 7, 2020. The high observed rate of venous thromboembolism prompted us to increase the prophylactic doses of enoxaparin from 40 mg daily up to 1 mg/kg twice daily in patients admitted to intensive care units (ICU), 0.7 mg/kg twice daily in high-intensity of care wards and 1 mg/kg daily in low-intensity of care wards. Patients on high enoxaparin doses were compared to those who received prophylaxis with the standard dosage. Efficacy endpoints were mortality, clinical deterioration, and the occurrence of venous thromboembolism, safety endpoint was the occurrence of major bleeding. Of 278 patients with Covid-19, 127 received prophylaxis with high enoxaparin doses and 151 with standard dosage. At 21 days, the incidence rate of death and clinical deterioration were lower in patients on higher doses than in those on the standard dosage (hazard ratio 0.39, 95% confidence interval 0.23-0.62), and the incidence of venous thromboembolism was also lower (hazard ratio 0.52, 95% confidence interval 0.26-1.05). Major bleeding occurred in four of 127 patients (3.1%) on the high enoxaparin dosage. In conclusion, in the cohort of patients with Covid-19 treated with high enoxaparin dosages we observed a 60% reduction of mortality and clinical deterioration and a 50% reduction of venous thromboembolism compared to standard dosage prophylaxis. However, 3% of patients on high enoxaparin dosages had non-fatal major bleeding.

Chronic comorbidities and clinical outcomes in patients with and without COVID-19: a large population-based study using national administrative healthcare open data of Mexico.

Abstract: Coronavirus disease 2019 (COVID-19) was rapidly expanded worldwide within a short period. Its relationship with chronic comorbidities is still unclear. We aimed to determine the effects of chronic comorbidities on clinical outcomes of patients with and without COVID-19. This was an analysis of 65,535 patients with suspicion of viral respiratory disease (38,324 SARS-CoV-2 positive and 27,211 SARS-CoV-2 negative) from January 01 to May 12, 2020 using the national administrative healthcare open data of Mexico. SARS-CoV-2 infection was confirmed by reverse-transcriptase–polymerase-chain-reaction. General characteristics and chronic comorbidities were explored. Clinical outcomes of interest were hospital admission, pneumonia, intensive care unit admission, endotracheal intubation and mortality. Prevalence of chronic comorbidities was 49.4%. Multivariate logistic regression analysis showed that the effect of age, male sex, bronchial asthma, diabetes mellitus and chronic kidney disease on clinical outcomes was similar for both SARS-CoV-2 positive and negative patients. Adverse clinical outcomes were associated with the time from symptoms onset to medical contact, chronic obstructive pulmonary disease, hypertension and obesity in SARS-CoV-2 positive patients, but with cardiovascular disease in SARS-CoV-2 negative patients (p value < 0.01 for all comparisons). Chronic comorbidities are commonly found in patients with suspicion of viral respiratory disease. The knowledge of the impact of comorbidities on adverse clinical outcomes can better define those COVID-19 patients at higher risk. The different impact of the specific type of chronic comorbidity on clinical outcomes in patients with and without SARS-CoV-2 infection requires further researches. These findings need confirmation using other data sources.

After the first wave and beyond lockdown: long-lasting changes in emergency department visit number, characteristics, diagnoses, and hospital admissions.

Abstract: The first wave (FW) of COVID-19 led to a rapid reduction in total emergency department (ED) visits and hospital admissions for other diseases. Whether this represented a transient "lockdown and fear" phenomenon, or a more persisting trend, is unknown. We divided acute from post-wave changes in ED flows, diagnoses, and hospital admissions, in an Italian city experiencing a FW peak followed by nadir. This multicenter, retrospective, cross-sectional study involved five general EDs of a large Italian city (January-August 2020). Percent changes were calculated versus 2019, using four 14-day periods (FW peak, early/mid/late post-wave). ED visits were 147,446 in 2020, versus 214,868 in 2019. During the FW peak, visits were reduced by 66.4% (P < 0.001). The drop was maximum during daytime (69.8%) and for pediatric patients (89.4%). Critical triage codes were unchanged. Reductions were found for all non-COVID-19 diagnoses. Non-COVID-19 hospital admissions were reduced by 39.5% (P < 0.001), involving all conditions except hematologic, metabolic/endocrine, respiratory diseases, and traumas. In the early, mid, and late post-wave periods, visits were reduced by 25.4%, 25.3% and 23.5% (all P < 0.001) respectively. In the late period, reduction was greater for female (27.9%) and pediatric patients (44.6%). Most critical triage codes were unchanged. Oncological, metabolic/endocrine, and hematological diagnoses were unchanged, while other diagnoses had persistent reductions. Non-COVID-19 hospital admissions were reduced by 12.8% (P = 0.001), 6.3% (P = 0.1) and 12.2% (P = 0.001), respectively. Reductions in ED flows, led by non-critical codes, persisted throughout the summer nadir of COVID-19. Hospital admissions for non-COVID-19 diseases had transient changes.

Timing of corticosteroids impacts mortality in hospitalized COVID-19 patients.

Abstract: The optimal timing of initiating corticosteroid treatment in hospitalized patients is unknown. We aimed to assess the relationship between timing of initial corticosteroid treatment and in-hospital mortality in COVID-19 patients. In this observational study through medical record analysis, we quantified the mortality benefit of corticosteroids in two equally matched groups of hospitalized COVID-19 patients. We subsequently evaluated the timing of initiating corticosteroids and its effect on mortality in all patients receiving corticosteroids. Demographic, clinical, and laboratory variables were collected and employed for multivariable regression analyses. 1461 hospitalized patients with confirmed COVID-19 were analyzed. Of these, 760 were also matched into two equal groups based on having received corticosteroid therapy. Patients receiving corticosteroids had a lower risk of death than those who did not (HR 0.67, 95% CI 0.67–0.90; p = 0.01). Timing of corticosteroids was assessed for all 615 patients receiving corticosteroids during admission. Patients receiving first dose of corticosteroids > 72 h into hospitalization had a lower risk of death compared to patients with first dose at earlier time intervals (HR 0.56, 95% CI 0.38–0.82; p = 0.003). There was a mortality benefit in patients with > 7 days of symptom onset to initiation of corticosteroids (HR 0.56, 95% CI 0.33–0.95; p = 0.03). In patients receiving oxygen therapy, corticosteroids reduced risk of death in mechanically ventilated patients (HR 0.38, 95% CI 0.24–0.60; p 7 days should trigger initiation of corticosteroids. In the absence of invasive mechanical ventilation, corticosteroids should be initiated if the patient remains hospitalized at 72 h. Hypoxia requiring supplemental oxygen therapy should not be a trigger for initiation of corticosteroids unless the timing is appropriate.

Role of ROX index in the first assessment of COVID-19 patients in the emergency department.

Abstract: During the first outbreak of Coronavirus disease 2019 (COVID-19) Emergency Departments (EDs) were overcrowded. Hence, the need for a rapid and simple tool to support clinical decisions, such as the ROX index (Respiratory rate – OXygenation), defined as the ratio of peripheral oxygen saturation and fraction of inspired oxygen, to respiratory rate. The aim of the study was to evaluate the accuracy of the ROX index in predicting hospitalization and mortality in patients with a diagnosis of COVID-19 in the ED. The secondary outcomes were to assess the number of readmissions and the variations in the ROX index between the first and the second admission. This was an observational prospective monocentric study, carried out in the ED of Sant’Orsola-Malpighi Hospital in Bologna, Italy. Five hundred and fifty-four consecutive patients with COVID-19 were enrolled and the ROX index was calculated. Patients were followed until hospital discharge or death. A ROX index value < 25.7 was associated with hospitalization (area under the curve [AUC] = 0.737, 95% CI 0.696–0.779, p < 0.001). The ROX index < 22.3 was statistically related to higher 30-day mortality (AUC = 0.764, 95% CI 0.708–0.820, p < 0.001). Eight patients were discharged and returned to the ED within the subsequent 7 days, their mean ROX index was 30.3 (6.2; range 21.9–39.4) at the first assessment and 24.6 (5.5; 14.5–29.5) at the second assessment, (p = 0.012). The ROX index, together with laboratory, imaging and clinical findings, correlated with the need for hospital admission, mechanical ventilation and mortality risk in COVID-19 patients.

Response to BNT162b2 mRNA COVID-19 vaccine among healthcare workers in Italy: a 3-month follow-up.

Abstract: This study investigated the response to BNT162b2 mRNA COVID-19 vaccine among healthcare workers (HCWs) in an Italian teaching hospital. 444 participants were surveyed with either multiple RT-PCR assays for detection of SARS-CoV-2 nucleic acid in nasopharyngeal swabs or serology testing for the research of virus-specific immunoglobulins. Adverse events following immunization (AEFI) were reported. Two weeks after the first dose anti-SARS-CoV-2 antibodies exceeded reactivity cut-off in 82.5% the participants. Four HCWs tested positive at nasopharyngeal swab after 3 months. More than three-quarters reported AEFIs. Our findings offer an insight regarding the vaccine response after 3 months from its administration, with a special focus on effectiveness data, as well as the type and number of AEFIs complained by HCW recipients. The presented study may serve as reference for future research which will be necessary to explore the long-term safety of this vaccine, especially in population at high risk for infection, such as HCWs.

Echocardiographic assessment of the right ventricle in COVID -related acute respiratory syndrome.

Abstract: In patients with the novel coronavirus (COVID-19) infection, the echocardiographic assessment of the right ventricle (RV) represents a pivotal element in the understanding of current disease status and in monitoring disease progression. The present manuscript is aimed at specifically describing the echocardiographic assessment of the right ventricle, mainly focusing on the most useful parameters and the time of examination. The RV direct involvement happens quite often due to preferential lung tropism of COVID-19 infection, which is responsible for an interstitial pneumonia characterized also by pulmonary hypoxic vasoconstriction (and thus an RV afterload increase), often evolving in acute respiratory distress syndrome (ARDS). The indirect RV involvement may be due to the systemic inflammatory activation, caused by COVID-19, which may affect the overall cardiovascular system mainly by inducing an increase in troponin values and in the sympathetic tone and altering the volemic status (mainly by affecting renal function). Echocardiographic parameters, specifically focused on RV (dimensions and function) and pulmonary circulation (systolic pulmonary arterial pressures, RV wall thickness), are to be measured in a COVID-19 patient with respiratory failure and ARDS. They have been selected on the basis of their feasibility (that is easy to be measured, even in short time) and usefulness for clinical monitoring. It is advisable to measure the same parameters in the single patient (based also on the availability of valid acoustic windows) which are identified in the first examination and repeated in the following ones, to guarantee a reliable monitoring. Information gained from a clinically-guided echocardiographic assessment holds a clinical utility in the single patients when integrated with biohumoral data (indicating systemic activation), blood gas analysis (reflecting COVID-19-induced lung damage) and data on ongoing therapies (in primis ventilatory settings).

Effectiveness and safety of noninvasive positive pressure ventilation in the treatment of COVID-19-associated acute hypoxemic respiratory failure: a single center, non-ICU setting experience

Abstract: The role of noninvasive positive pressure ventilation (NIPPV) in COVID-19 patients with acute hypoxemic respiratory failure (AHRF) is uncertain, as no direct evidence exists to support NIPPV use in such patients. We retrospectively assessed the effectiveness and safety of NIPPV in a cohort of COVID-19 patients consecutively admitted to the COVID-19 general wards of a medium-size Italian hospital, from March 6 to May 7, 2020. Healthcare workers (HCWs) caring for COVID-19 patients were monitored, undergoing nasopharyngeal swab for SARS-CoV-2 in case of onset of COVID-19 symptoms, and periodic SARS-CoV-2 screening serology. Overall, 50 patients (mean age 74.6 years) received NIPPV, of which 22 (44%) were successfully weaned, avoiding endotracheal intubation (ETI) and AHRF-related death. Due to limited life expectancy, 25 (50%) of 50 NIPPV-treated patients received a “do not intubate” (DNI) order. Among these, only 6 (24%) were weaned from NIPPV. Of the remaining 25 NIPPV-treated patients without treatment limitations, 16 (64%) were successfully weaned, 9 (36%) underwent delayed ETI and, of these, 3 (33.3%) died. NIPPV success was predicted by the use of corticosteroids (OR 15.4, CI 1.79–132.57, p 0.013) and the increase in the PaO2/FiO2 ratio measured 24–48 h after NIPPV initiation (OR 1.02, CI 1–1.03, p 0.015), while it was inversely correlated with the presence of a DNI order (OR 0.03, CI 0.001–0.57, p 0.020). During the study period, 2 of 124 (1.6%) HCWs caring for COVID-19 patients were diagnosed with SARS-CoV-2 infection. Apart from patients with limited life expectancy, NIPPV was effective in a substantially high percentage of patients with COVID-19-associated AHRF. The risk of SARS-CoV-2 infection among HCWs was low.

Atrial fibrillation pattern and factors affecting the progression to permanent atrial fibrillation

Abstract: Atrial fibrillation (AF) may progress from a non-permanent to a permanent form, and improvement in prediction may help in decision-making. In- and outpatients with non-permanent AF were enrolled in a prospective study and followed every 6 months. At baseline, 314 out of 523 patients (60%) had non-permanent AF (25.5% paroxysmal AF, 52.5% persistent, 2% first diagnosed AF). They were mostly males (188, 59.9%), median age 71 years [interquartile range (IQ) 62–77], median CHA2DS2VASc 3 (IQ 1–4), median HATCH score 1 (IQ 1–2). During a follow-up of 701 (IQ 437–902) days, 66 patients (21%) developed permanent AF. CHA2DS2VASc and HATCH scores were incrementally associated with AF progression (p for trend CHA2DS2VASc 2 (HR 0.358, 95%CI 0.162–0.791, p = 0.011) and valvular disease (HR 2.196, 95%CI 1.072–4.499, p = 0.032) were significantly associated with AF progression. Adding “moderate–severe LA dilation” to clinical scores, eg. HATCH score (HATCH-LA) with 2 points (Cox multivariable regression analysis) improved prediction of AF progression vs. HATCH score (p = 0.0225). In patients without permanent AF, progression of AF was independently associated with age, LA dilation, AF symptoms severity, antiarrhythmic drugs and valvular disease. Adding LA dilation (moderate–severe volume increase) to clinical scores improved prediction of progression to permanent AF.

Adverse drug reactions in SARS-CoV-2 hospitalised patients: a case-series with a focus on drug-drug interactions.

Abstract: Due to the need of early and emergency effective treatments for COVID-19, less attention may have been paid to their safety during the global emergency. In addition, characteristics of drug-drug interaction (DDI)-related adverse drug reactions (ADRs) in COVID-19 patients have not yet been studied in depth. The aim of the present case-series study is to describe clinical and pharmacological characteristics of SARS-CoV-2 hospitalised patients, focusing on ADRs, particularly those related to DDIs. We evaluated all reports of COVID-19 medication-related ADRs collected within the COVID-19 Units of Careggi University Hospital, Florence (Italy), between January 1st and 31st May 2020. Information regarding COVID-19 medications, patients' demographic and clinical characteristics, concomitant drugs, ADRs description and outcome, were collected. Each case was evaluated for the causality assessment and to identify the presence of DDIs. During the study period, 23 Caucasian patients (56.5% males, mean age 76.1 years) experienced one or more ADRs. The majority of them were exposed to polypharmacy and 17.4% presented comorbidities. ADRs were referred to cardiovascular, psychiatric and gastrointestinal disorders. The most frequently reported preferred term was QT prolongation (mean QT interval 496.1 ms). ADRs improved or resolved completely in 60.8% of cases. For all patients, a case-by-case evaluation revealed the presence of one or more DDIs, especially those related to pharmacokinetic interactions. Despite the small number of patients, our evidence underline the clinical burden of DDIs in SARS-CoV-2 hospitalised patients and the risk of unexpected and uncommon psychiatric ADRs.