Experience With Hydroxychloroquine and Azithromycin in the Coronavirus Disease 2019 Pandemic: Implications for QT Interval Monitoring.

Background Despite a lack of clinical evidence, hydroxychloroquine and azithromycin are being administered widely to patients with verified or suspected coronavirus disease 2019 (COVID-19). Both drugs may increase risk of lethal arrhythmias associated with QT interval prolongation. Methods and Results We analyzed a case series of COVID-19-positive/suspected patients admitted between February 1, 2020, and April 4, 2020, who were treated with azithromycin, hydroxychloroquine, or a combination of both drugs. We evaluated baseline and postmedication QT interval (corrected QT interval [QTc]; Bazett) using 12-lead ECGs. Critical QTc prolongation was defined as follows: (1) maximum QTc ≥500 ms (if QRS <120 ms) or QTc ≥550 ms (if QRS ≥120 ms) and (2) QTc increase of ≥60 ms. Tisdale score and Elixhauser comorbidity index were calculated. Of 490 COVID-19-positive/suspected patients, 314 (64%) received either/both drugs and 98 (73 COVID-19 positive and 25 suspected) met study criteria (age, 62±17 years; 61% men). Azithromycin was prescribed in 28%, hydroxychloroquine in 10%, and both in 62%. Baseline mean QTc was 448±29 ms and increased to 459±36 ms (P=0.005) with medications. Significant prolongation was observed only in men (18±43 ms versus -0.2±28 ms in women; P=0.02). A total of 12% of patients reached critical QTc prolongation. Changes in QTc were highest with the combination compared with either drug, with much greater prolongation with combination versus azithromycin (17±39 ms versus 0.5±40 ms; P=0.07). No patients manifested torsades de pointes. Conclusions Overall, 12% of patients manifested critical QTc prolongation, and the combination caused greater prolongation than either drug alone. The balance between uncertain benefit and potential risk when treating COVID-19 patients should be carefully assessed.

Cardiac arrhythmias in hospitalized patients with COVID-19: A prospective observational study in the western United States.

Arrhythmias have been reported frequently in COVID-19 patients, but the incidence and nature have not been well characterized. Patients admitted with COVID-19 and monitored by telemetry were prospectively enrolled in the study. Baseline characteristics, hospital course, treatment and complications were collected from the patients' medical records. Telemetry was monitored to detect the incidence of cardiac arrhythmias. The incidence and types of cardiac arrhythmias were analyzed and compared between survivors and non-survivors. Among 143 patients admitted with telemetry monitoring, overall in-hospital mortality was 25.2% (36/143 patients) during the period of observation (mean follow-up 23.7 days). Survivors were less tachycardic on initial presentation (heart rate 90.6 ± 19.6 vs. 99.3 ± 23.1 bpm, p = 0.030) and had lower troponin (peak troponin 0.03 vs. 0.18 ng/ml. p = 0.004), C-reactive protein (peak C-reactive protein 97 vs. 181 mg/dl, p = 0.029), and interleukin-6 levels (peak interleukin-6 30 vs. 246 pg/ml, p = 0.003). Sinus tachycardia, the most common arrhythmia (detected in 39.9% [57/143] of patients), occurred more frequently in non-survivors (58.3% vs. 33.6% in survivors, p = 0.009). Premature ventricular complexes occurred in 28.7% (41/143), and non-sustained ventricular tachycardia in 15.4% (22/143) of patients, with no difference between survivors and non-survivors. Sustained ventricular tachycardia and ventricular fibrillation were not frequent (seen only in 1.4% and 0.7% of patients, respectively). Contrary to reports from other regions, overall mortality was higher and ventricular arrhythmias were infrequent in this hospitalized and monitored COVID-19 population. Either disease or management-related factors could explain this divergence of clinical outcomes, and should be urgently investigated.

Pre-existing traits associated with Covid-19 illness severity.

IMPORTANCE: Certain individuals, when infected by SARS-CoV-2, tend to develop the more severe forms of Covid-19 illness for reasons that remain unclear. OBJECTIVE: To determine the demographic and clinical characteristics associated with increased severity of Covid-19 infection. DESIGN: Retrospective observational study. We curated data from the electronic health record, and used multivariable logistic regression to examine the association of pre-existing traits with a Covid-19 illness severity defined by level of required care: need for hospital admission, need for intensive care, and need for intubation. SETTING: A large, multihospital healthcare system in Southern California. PARTICIPANTS: All patients with confirmed Covid-19 infection (N = 442). RESULTS: Of all patients studied, 48% required hospitalization, 17% required intensive care, and 12% required intubation. In multivariable-adjusted analyses, patients requiring a higher levels of care were more likely to be older (OR 1.5 per 10 years, P<0.001), male (OR 2.0, P = 0.001), African American (OR 2.1, P = 0.011), obese (OR 2.0, P = 0.021), with diabetes mellitus (OR 1.8, P = 0.037), and with a higher comorbidity index (OR 1.8 per SD, P<0.001). Several clinical associations were more pronounced in younger compared to older patients (Pinteraction<0.05). Of all hospitalized patients, males required higher levels of care (OR 2.5, P = 0.003) irrespective of age, race, or morbidity profile. CONCLUSIONS AND RELEVANCE: In our healthcare system, greater Covid-19 illness severity is seen in patients who are older, male, African American, obese, with diabetes, and with greater overall comorbidity burden. Certain comorbidities paradoxically augment risk to a greater extent in younger patients. In hospitalized patients, male sex is the main determinant of needing more intensive care. Further investigation is needed to understand the mechanisms underlying these findings.

Allogeneic cardiosphere-derived cells (CAP-1002) in critically ill COVID-19 patients: compassionate-use case series.

There are no definitive therapies for patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Therefore, new therapeutic strategies are needed to improve clinical outcomes, particularly in patients with severe disease. This case series explores the safety and effectiveness of intravenous allogeneic cardiosphere-derived cells (CDCs), formulated as CAP-1002, in critically ill patients with confirmed coronavirus disease 2019 (COVID-19). Adverse reactions to CAP-1002, clinical status on the World Health Organization (WHO) ordinal scale, and changes in pro-inflammatory biomarkers and leukocyte counts were analyzed. All patients (n = 6; age range 19-75 years, 1 female) required ventilatory support (invasive mechanical ventilation, n = 5) with PaO2/FiO2 ranging from 69 to 198. No adverse events related to CAP-1002 administration were observed. Four patients (67%) were weaned from respiratory support and discharged from the hospital. One patient remains mechanically ventilated as of April 28th, 2020; all survive. A contemporaneous control group of critically ill COVID-19 patients (n = 34) at our institution showed 18% overall mortality at a similar stage of hospitalization. Ferritin was elevated in all patients at baseline (range of all patients 605.43-2991.52 ng/ml) and decreased in 5/6 patients (range of all patients 252.89-1029.90 ng/ml). Absolute lymphocyte counts were low in 5/6 patients at baseline (range 0.26-0.82 × 103/µl) but had increased in three of these five patients at last follow-up (range 0.23-1.02 × 103/µl). In this series of six critically ill COVID-19 patients, intravenous infusion of CAP-1002 was well tolerated and associated with resolution of critical illness in 4 patients. This series demonstrates the apparent safety of CAP-1002 in COVID-19. While this initial experience is promising, efficacy will need to be further assessed in a randomized controlled trial.

COVID-19 and the Heart.

Infection with the severe acute respiratory syndrome novel coronavirus produces a clinical syndrome known as 2019 novel coronavirus disease (COVID-19). When severe, COVID-19 is a systemic illness characterized by hyperinflammation, cytokine storm, and elevations of cardiac injury biomarkers. Here, we review what is known about the pathophysiology of COVID-19, its cardiovascular manifestations, and emerging therapeutic prospects. In this rapidly moving field, this review was comprehensive as of April 3, 2020.