Safety of ACEi and ARB in COVID-19 management: A retrospective analysis.

BACKGROUND & AIMS: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2)is a highly contagious virus that has infected 260 million individuals since December 2019. The severity of coronavirus disease 2019 (COVID-19) depends upon the complex interplay between viral factors and the host's inflammatory response, which can trigger a cascadeeventually leading to multiorgan failure. There is contradictory evidence that angiotensin-converting enzyme (ACEi) or angiotensin receptor blockers (ARBs) may affect mortality in patients with severe COVID-19, theoretically due to interaction with the bradykinin pathway. Therefore, we aim to explore the association between ACEi and ARB use and mortality in severe SARS-CoV2 infection.Severe acute respiratory yndrome with coronavirus (SARS-CoV2) is a highly contagious virus that has infected 260 million individuals since December 2019. The severity of COVID-19 depends upon the complex interplay between viral factors and the host's inflammatory response, which can trigger a cascadeeventually leading to multiorgan failure. There is contradictory evidence that angiotensin-converting enzyme (ACEi) or angiotensin receptor blockers (ARBs) may affect mortality in patients with severe COVID-19, theoretically due to interaction with the bradykinin pathway. Therefore, we aim to explore the association between ACEi and ARB use and mortality in severe SARS-CoV2 infection. MATERIALS & METHODOLOGY: This multicenter retrospective observational study enrolled 2935 COVID-19 patients admitted at six hospitals in Southern California, USA, between March 2020 and August 2021. Our primary outcome was the association of pre-hospital use of ACEi and ARB on in-hospital mortality in COVID-19 patients. First, relevant deidentified patient data were extracted using an SQL program from the electronic medical record. Then, a bivariate analysis of the relationship between ACEi and ARB use and different study variables using χ2 and t test was done. Finally, we did a backward selection Cox multivariate regression analysis using mortality as a dependent variable. RESULTS: Of the 2935 patients in the study, hypertension was present in 40.6%, and congestive heart failure in 13.8%. ACEi and ARB were used by 17.5% and 11.3% of patients, respectively, with 28.8% of patients on either medication. After adjusting for confounding variables in the multivariate analysis, the use of ACEi (HR: 1.226, 95% CI: 0.989-1.520) or ARB (HR: 0.923, 95% CI: 0.701-1.216) was not independently associated with increased mortality. CONCLUSION: Our results are consistent with the clinical guidelines and position statements per the International Society of Hypertension, that there is no indication to stop the use of ACEi/ARB in COVID-19 patients.

A Multicenter Retrospective Analysis on the Etiology of Bradycardia in COVID-19 Patients.

Introduction Bradycardia has been reported in the setting of SARS-CoV2 (COVID-19) and appears to be an important cardiac manifestation with an association of mortality. However, the etiology of bradycardia in COVID-19 remains unclear. Therefore, this study aims to retrospectively investigate the potential causes of bradycardia in COVID-19 patients. Method The multicenter retrospective analysis consisted of 1,116 COVID-19 positive patients from March 2020 to March 2021. Bradycardia and severe bradycardia were defined as a sustained heart rate of <60 BPM and <50 BPM, respectively, on two separate occasions, a minimum of four hours apart during the hospitalization. End-of-life bradycardia was excluded from the study. Data were retrieved using a structured query language (SQL) program through the EMR, and data were analyzed using IBM SPSS 27.0 (IBM Corp., Armonk, NY). Logistic regression was used to study the bradycardic event and its association with remdesivir, beta-blockers, or steroids use during the patient's hospital stay. Result In the multivariate analysis, bradycardia was significantly associated with length of hospital stay (p<0.001), mortality (p=0.022), ventilator use (p=0.001), and steroid use (p=0.001). However, there was no significant association between bradycardia and remdesivir use (p=0.066) or beta-blocker use (p=0.789). Conclusion Our study showed that steroid use was protective against developing bradycardia in COVID-19 patients. Furthermore, remdesivir and the use of beta-blockers were not associated with bradycardia in COVID-19 patients. However, bradycardia was associated with both increased mortality and length of stay in the hospital. Therefore, future studies should focus on the mechanism of bradycardia in COVID-19 patients and the effect of bradycardia on patient outcomes.

Predictors of Mortality in COVID-19 Patients in Southern California - Retrospective Multicenter Study.

Introduction The majority of patients infected with coronavirus disease 2019 (COVID-19) recover from the illness after suffering mild to moderate symptoms, while approximately 20% progress to severe or critical disease, which may result in death. Understanding the predictors of severe disease and mortality in COVID-19 patients will help to risk stratify patients and improve clinical decision making. US data to inform this understanding are, however, scarce. We studied predictors of COVID-19 mortality in a cohort of 1,116 hospitalized patients in Southern California in the United States. Methods We conducted a retrospective cohort study of COVID-19 patients admitted at two hospitals in Southern California United States between March 2020 and March 2021. Bivariate and multivariate analyses of the relationship between mortality and other variables such as demographics, comorbidities, and laboratory values were performed, with a p-value of 0.05 considered as significant. Results The analysis involved 1,116 COVID-19 patients, of which 51.5% were males and 48.5% were females. Of the 1,116 patients, 81.6% were whites, 7.2% were blacks, and 11.2% were other races. After adjusting for co-variables, age (p<0.001), admission to intensive care unit (p< 0.001), use of remdesivir (p=0.018), C-reactive protein (CRP) levels (p<0.001), and lactate dehydrogenase (LDH) levels (p=0.039) were independently associated with mortality in our study. Gender, race, body mass index, presence of co-morbidities such as diabetes and hypertension, and use of steroid, statin, calcium channel blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers were not associated with mortality in the multivariate analysis. Conclusion In the cohort we studied, admission to intensive care unit was associated with decreased mortality while older age, use of remdesivir, and high levels of CRP and LDH were associated with increased mortality in COVID-19 patients.

A novel study on SARS-COV-2 virus associated bradycardia as a predictor of mortality-retrospective multicenter analysis.

BACKGROUND: SARS-CoV2 has affected more than 73.8 million individuals. While SARS-CoV2 is considered a predominantly respiratory virus, we report a trend of bradycardia among hospitalized patients, particularly in association with mortality. METHODOLOGY: The multi-center retrospective analysis consisted of 1053 COVID-19 positive patients from March to August 2020. A trend of bradycardia was noted in the study population. Absolute bradycardia and profound bradycardia was defined as a sustained heart rate < 60 BPM and < 50 BPM, respectively, on two separate occasions, a minimum of 4 h apart during hospitalization. Each bradycardic event was confirmed by two physicians and exclusion criteria included: less than 18 years old, end of life bradycardia, left AMA, or taking AV Nodal blockers. Data was fetched using a SQL program through the EMR and data was analyzed using SPSS 27.0. A logistic regression was done to study the effect of bradycardia, age, gender, and BMI on mortality in the study group. RESULTS: 24.9% patients had absolute bradycardia while 13.0% had profound bradycardia. Patients with absolute bradycardia had an odds ratio of 6.59 (95% CI [2.83-15.36]) for mortality compared with individuals with a normal HR response. The logistic regression model explained 19.6% (Nagelkerke R2 ) of variance in the mortality, correctly classified 88.6% of cases, and was statistically significant X2 (5)=47.10, p < .001. For each year of age > 18, the odds of dying increased 1.048 times (95% CI [1.25-5.27]). CONCLUSION: The incidence of absolute bradycardia was found in 24.9% of the study cohort and these individuals were found to have a significant increase in mortality.

Use of Baricitinib in Combination With Remdesivir and Steroid in COVID-19 Treatment: A Multicenter Retrospective Study.

Introduction Hospitalized patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can develop severe complications. Baricitinib, a Janus kinase (JAK) JAK1/JAK2 inhibitor used to treat rheumatoid arthritis, has been proposed to prevent intracellular uptake of SARS-CoV-2 by targeting the angiotensin-converting enzyme 2 (ACE2) receptor, suppressing cytokine storm. We evaluated the effects of baricitinib on coronavirus disease 2019 (COVID-19) patient survival. Methods We conducted a retrospective study of 100 COVID-19 patients hospitalized in Southern California, United States, throughout September 2021. Univariate analysis of study variables was conducted with bivariate analysis of their relationships using chi-square and t-test with p-value <0.05 considered significant. Kaplan-Meier survival analysis was performed to compare outcomes of COVID-19 patients treated with baricitinib and those that were not. Results Our study included a patient population with a mean age of 62 years. Twenty-four percent of our patients were admitted to the intensive care unit (ICU), 16% were placed on mechanical ventilation, and 27% were expired. Patients receiving baricitinib were more likely to be admitted to the ICU and receive concomitant remdesivir therapy. Use of baricitinib increased median survival (p = 0.045). Conclusion Baricitinib administered with remdesivir and dexamethasone was shown to increase the survival of hospitalized patients with COVID-19. More studies are required to evaluate the benefits of conjunctive therapy with baricitinib, remdesivir, and dexamethasone. Though our study shows increased survival in patients receiving therapy, our study is limited by small sample size and there was not enough data to confirm whether baricitinib therapy decreased disease progression. Further studies are required.