Impact of prior statin use on clinical outcomes in COVID-19 patients: data from tertiary referral hospital during COVID-19 pandemic in Italy

Aims Epidemiological evidence suggests that anti-inflammatory and immuno-modulatory properties of statins may reduce the risk of infections and infection-related complications. In this observational multi-centre study, we aimed to assess the impact of prior statin use on coronavirus disease (COVID-19) severity and mortality. Methods and results Consecutive patients hospitalized for COVID-19 were considered and enrolled in four tertiary referral hospitals (Luigi Sacco Hospital, Milan;Policlinico Umberto I Hospital, Rome;Spedali Civili Hospital, Brescia;Humanitas Gavazzeni Hospital;Bergamo) From 23 February 2020 to 31 March 2020, in-hospital mortality and severity of COVID-19 assessed with National Early Warning Score (NEWS) were deemed primary and secondary outcomes, respectively. Among 842 patients enrolled, 179 (21%) were treated with statins before admission. Statin patients showed more comorbidities and more severe COVID-19 [NEWS 4 (IQR: 2–6) vs. 3 (IQR: 2–5), P < 0.001]. Despite having similar rates of intensive care unit admission, noninvasive ventilation, and mechanical ventilation, statin users appeared to show higher mortality rates. After balancing pre-existing relevant clinical conditions that could affect COVID-19 prognosis with propensity score matching, statin therapy confirmed its association with a more severe disease (NEWS ≥ 5;61% vs. 48%, P = 0.025) but not with in-hospital mortality (26% vs. 28%, P = 0.185). At univariate logistic regression analysis, statin use was confirmed not to be associated with mortality (OR: 0.901;95% CI: 0.537–1.51;P = 0.692) and to be associated with a more severe disease (NEWS ≥ 5 OR: 1.7;95% CI: 1.067–2.71;P = 0.026). Conclusions Our results did not confirm the supposed favourable effects of statin therapy on COVID-19 outcomes. Conversely, they suggest that statin use should be considered as a proxy of underlying comorbidities, which indeed expose to increased risks of more severe COVID-19.538 Figure 1

Assessment of long-term arrhytmic sequelae in patients recovering from COVID-19 infection

Aims COVID-19 has been associated with acute cardiac complications including cardiac arrhythmias. We aimed to assess the prevalence of long-term cardiac arrhythmias in patients recovering from severe COVID-19 infection with proved or suspected of cardiac involvement. Methods and results All patients with COVID-19 infection discharged from the cardiology department of our institution from the 1 March to the 30 April 2020 were considered eligible for this study. Patients were fitted out with an adhesive patch and a wireless single-lead 24-h electrocardiogram (ECG) Holter monitor (Rooti Rx® System, Rooti Labs Ltd, Taipei, Taiwan). RootiRx® is a small device consisting of an integrated sensor system, a microelectronic board with memory storage, and an internal rechargeable battery. This system can provide continuous ECG and was set to monitor heart rhythm for 24 h. The Holter system provides also blood pressure measurements and sleep apnea data which are evaluated through chest wall motion/cyclic variation of heart rate and reported along with the sleep efficiency (percentage of time spent asleep while in bed). Arrhythmic findings, sleep apnea detections, and residual COVID-19 symptoms were reported. The study follow-up was performed 174 (range = 166–190) days after hospital discharge in a cohort of 63 (76% males, median age 66 years) patients. New diagnosis of atrial fibrillation (AF) was performed in three sinus rhythm patients (4.8%). Eleven (18%) patients had asymptomatic bradycardia (<45 b.p.m.) with no pauses lasting more than 3 s. Non-sustained ventricular tachycardia (<30 s) episodes were recorded in two (3.2%) patients, while no sustained ventricular arrhythmia was documented. The Holter system indicated the presence of moderate-to-severe obstructive sleep apnea episodes in 33 (53%) patients without known history of sleep disorders. Some previously unrecognized long-lasting COVID-19 symptoms were also described: fatigue (10, 16%), myalgia (3, 4.8%), and impaired attention (1, 1.6%). Conclusions Six months after the infection, we performed new diagnoses of AF in patients who recovered from severe COVID-19 infection with proved or suspected cardiac involvement using 24-h Holter monitoring. No other arrhythmias were observed, but the Holter system identified obstructive sleep apnea episodes in half of the patients. A relevant percentage of patients also described persisting symptoms of COVID-19 infection. These findings suggest further prospective studies to better describe long-term arrhythmic manifestations and residual symptoms in patients hospitalized with COVID-19 infection.

Reduction of admissions for urgent and elective pacemaker implant during the COVID-19 outbreak in Northern Italy.

AIMS: The coronavirus disease-19 (COVID-19) outbreak has been recently associated with lower hospitalization rates for acute coronary syndromes. Aim of the study was to investigate whether a similar behaviour is observed in admissions for urgent pacemaker implant. METHODS: This retrospective study included 1315 patients from 18 hospitals in Northern Italy with a high number of COVID-19 cases. Hospitalization rates for urgent pacemaker implant were compared between the following periods: 20 February to 20 April 2020 (case period); from 1 January to 19 February 2020 (intra-year control period); from 20 February to 20 April 2019 (inter-year control period). RESULTS: The incidence rate of urgent implants was 5.0/day in the case period, 6.0/day in the intra-year control period and 5.8/day in the inter-year control period. Incidence rate in the case period was significantly lower than both the intra-year [incidence rate ratio (IRR): 0.81, 95% CI 0.67-0.99, P = 0.040] and inter-year control periods (IRR: 0.79, 95% CI 0.66-0.95, P = 0.012); this reduction was highest after the national lockdown (IRR 0.68, 95% CI 0.52-0.91, P = 0.009). The prevalence of residents in rural areas undergoing urgent pacemaker implant was lower in the case period (36%) than in both the intra-year (47%, P = 0.03) and inter-year control periods (51%, P = 0.002). Elective pacemaker implants also decreased in the case period, with the incidence rate here being 3.5/day vs. 6.4/day in the intra-year (-45%) and 6.9/day in the inter-year period (-49%). CONCLUSION: Despite severe clinical patterns, the COVID-19 outbreak has negatively affected the population presentation to Emergency Departments for bradyarrhythmias requiring urgent pacemaker implant in Northern Italy. This mainly occurred after the national lockdown and concerned patients living in rural areas.

Prevalence and outcome of silent hypoxemia in COVID-19.

BACKGROUND: In the early stages of COVID-19 pneumonia, hypoxemia has been described in absence of dyspnea ("silent" or "happy" hypoxemia). Our aim was to report its prevalence and outcome in a series of hypoxemic patients upon Emergency Department admission. METHODS: In this retrospective observational cohort study we enrolled a study population consisting of 213 COVID-19 patients with PaO2/FiO2 ratio <300 mmHg at hospital admission. Two groups (silent and dyspneic hypoxemia) were defined. Symptoms, blood gas analysis, chest X-ray (CXR) severity, need for intensive care and outcome were recorded. RESULTS: Silent hypoxemic patients (68-31.9%) compared to the dyspneic hypoxemic patients (145-68.1%) showed greater frequency of extra respiratory symptoms (myalgia, diarrhea and nausea) and lower plasmatic LDH. PaO2/FiO2 ratio was 225±68 mmHg and 192±78 mmHg in silent and dyspneic hypoxemia respectively (P=0.002). Eighteen percent of the patients with PaO2/FiO2 from 50 to 150 mmHg presented silent hypoxemia. Silent and dyspneic hypoxemic patients had similar PaCO2 (34.2±6.8 mmHg vs. 33.5±5.7 mmHg, P=0.47) but different respiratory rates (24.6±5.9 bpm vs. 28.6±11.3 bpm respectively, P=0.002). Even when CXR was severely abnormal, 25% of the population was silent hypoxemic. Twenty-six point five percent and 38.6% of silent and dyspneic patients were admitted to the ICU respectively (P=0.082). Mortality rate was 17.6% and 29.7% (log-rank P=0.083) in silent and dyspneic patients. CONCLUSIONS: Silent hypoxemia is remarkably present in COVID-19. The presence of dyspnea is associated with a more severe clinical condition.

Use of a novel implantable cardioverter-defibrillator multisensor algorithm for heart failure monitoring in a COVID-19 patient: A case report.

We report the case of a patient implanted with an implantable defibrillator endowed with a multisensor algorithm for heart failure monitoring. Automatic measurement of multiple clinical variables allowed to detect impending heart failure decompensation and showed its ability to facilitate differential diagnosis in the context of the current COVID-19 pandemic.

Oral anticoagulation and clinical outcomes in COVID-19: An Italian multicenter experience.

BACKGROUND: Since the body of evidence addressing the coagulation derangements caused by Coronavirus disease (COVID-19) has been constantly growing, we investigated whether pre-hospitalization oral anticoagulation (OAC) or in-hospital heparin treatment could have a protective role among COVID-19 patients. METHOD: In this cohort study, consecutive COVID-19 patients admitted to four different Italian Institutions were enrolled. Baseline demographic, clinical, laboratory, and radiological characteristics, as well as in-hospital treatment and outcomes were evaluated. The primary outcome was mortality. RESULTS: A total of 844 COVID-19 patients were enrolled as study cohort, n = 65 (7.7%) taking OACs prior to hospitalization. Regarding clinical outcomes, OAC patients developed acute hypoxemic respiratory failure (AHRF) more frequently than non-OAC patients as well as presenting a higher mortality rate (44.6% vs 19.8%, p < 0.001). At overall multivariate logistical regression, use of heparin (n = 394, 46.6%) was associated with a better chance of survival to hospital discharge (OR 0.60 [0.38-0.94], p < 0.001), in particular in patients with AHRF, with no association found with the use of OACs. In a sub-analysis, the highest mortality rate was found for AHRF patients when heparin was not administered. CONCLUSION: In our cohort, OACs appeared to be ineffective in reducing mortality rate, while heparin resulted to be a useful treatment when lung disease was sufficiently severe, potentially suggesting a crucial role of microthrombosis in severe COVID-19. Due to the relatively small number of COVID-19 patients treated with OACs included in our analysis and their higher number of comorbidities, larger studies are needed in order to confirm our findings.

Characteristics and outcomes of patients hospitalized for COVID-19 and cardiac disease in Northern Italy.

AIMS: To compare demographic characteristics, clinical presentation, and outcomes of patients with and without concomitant cardiac disease, hospitalized for COVID-19 in Brescia, Lombardy, Italy. METHODS AND RESULTS: The study population includes 99 consecutive patients with COVID-19 pneumonia admitted to our hospital between 4 March and 25 March 2020. Fifty-three patients with a history of cardiac disease were compared with 46 without cardiac disease. Among cardiac patients, 40% had a history of heart failure, 36% had atrial fibrillation, and 30% had coronary artery disease. Mean age was 67 ± 12 years, and 80 (81%) patients were males. No differences were found between cardiac and non-cardiac patients except for higher values of serum creatinine, N-terminal probrain natriuretic peptide, and high sensitivity troponin T in cardiac patients. During hospitalization, 26% patients died, 15% developed thrombo-embolic events, 19% had acute respiratory distress syndrome, and 6% had septic shock. Mortality was higher in patients with cardiac disease compared with the others (36% vs. 15%, log-rank P = 0.019; relative risk 2.35; 95% confidence interval 1.08-5.09). The rate of thrombo-embolic events and septic shock during the hospitalization was also higher in cardiac patients (23% vs. 6% and 11% vs. 0%, respectively). CONCLUSIONS: Hospitalized patients with concomitant cardiac disease and COVID-19 have an extremely poor prognosis compared with subjects without a history of cardiac disease, with higher mortality, thrombo-embolic events, and septic shock rates.

Sinus Node Dysfunction in a Young Patient With COVID-19.

A 34-year-old man was admitted with acute lung injury and COVID-19 pneumonia. In the intensive care unit, he experienced episodes of prolonged asystole accompanied by hypotension without loss of consciousness. Once reversible causes were excluded, symptoms were related to dysfunction of the sinus node, and the patient underwent implantation of a pacemaker. (Level of Difficulty: Beginner.).

Acute pulmonary embolism in COVID-19 disease: Preliminary report on seven patients.

There is some evidence that Covid 19 pneumonia is associated with prothrombotic status and increased risk of venous thromboembolic events (deep venous thrombosis and pulmonary embolism). Over a two-week period we admitted in our Unit 25 patients with Covid-19 pneumonia, of these pulmonary embolism was diagnosed using computed tomography angiography in 7. We report on clinical and biochemical features of these patients. They were all males, with a mean age of 70.3 years (range 58-84); traditional risk factors for venous thromboembolism were identified in the majority of patients with pulmonary embolism, however not differently from those without pulmonary embolism. Clinical presentation of pulmonary embolism patients was usually characterized by persistence or worsening of respiratory symptoms, with increasing oxygen requirement. D-dimer levels were several fold higher than the upper threshold of normal; in patients in whom PE was recognized during hospital stay, a rapid and relevant increase of D-dimer levels was observed. Computed tomographic findings ranged from massive acute pulmonary embolism to a segmental or sub-segmental pattern; furthermore, thrombosis of sub-segmental pulmonary arteries within lung infiltrates were occasionally seen, suggesting local mechanisms. Six out of 7 patients were treated with unfractionated or low molecular weight heparin with clinical benefit within few days; one patient needed systemic thrombolysis (death from hemorrhagic complication).