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There were no statistically significant differences in cardiac biomarkers or in electrocardiograms. We found no increased risk of ischemic heart injury or heart failure as a result of administering chloroquine. However, the use of chloroquine to treat COVID-19 outside of clinical trials is not recommended, considering the lack of evidence of its effectiveness, as well as the elevated risk of fatal arrythmias.

Citation: Beck-Friis J, Leach S, Omerovic E, Zeijlon R, Gisslen M, Yilmaz A (2021) No difference in biomarkers of ischemic heart injury and heart failure in patients with COVID-19 who received treatment with chloroquine phosphate and those who did not.

PLoS ONE 16(8): e0256035. Funding: This work was supported by the Swedish state, under an agreement between the Swedish government and the county councils (ALF agreement ALFGBG-717531 (MG) and ALFGBG-679621 (SL)); and by SciLifeLab Sweden (KAW 2020.

Coronavirus disease 2019 (COVID-19) is an infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with a symptomatology that varies from no (or very mild) symptoms in the upper airways to severe viral pneumonia with respiratory failure. Because of the immunomodulatory effects of chloroquine, these drugs have long been used to treat inflammatory diseases such as rheumatoid arthritis and systemic lupus erythematosus.

Since then, chloroquine has been used Drotrecogin alfa (Xigris)- FDA a varying degree in many countries, including Sweden. The Department of Infectious Diseases at Sahlgrenska Drotrecogin alfa (Xigris)- FDA Hospital, Gothenburg, discontinued the use of chloroquine phosphate at the end of March 2020 due to a lack of evidence regarding efficacy and the risk of severe adverse events.

To our knowledge, no studies of markers of cardiac injury during chloroquine treatment for COVID-19 have been published to date. The primary aim of our study was to examine whether patients with COVID-19 undergoing treatment with chloroquine phosphate had an increased risk of cardiotoxicity with regard Drotrecogin alfa (Xigris)- FDA ischemic heart injury, heart failure, and arrhythmias, when compared to patients receiving standard treatment.

This is a retrospective study of patients Drotrecogin alfa (Xigris)- FDA COVID-19 who received treatment with chloroquine phosphate (500 mg twice Brukinsa (Zanubrutini Capsules)- FDA and matched controls from the same Drotrecogin alfa (Xigris)- FDA period who did not Drotrecogin alfa (Xigris)- FDA chloroquine phosphate.

Inclusion criteria were a) confirmed diagnosis of COVID-19 by positive polymerase chain-reaction test (PCR) from the upper respiratory tract for SARS-CoV-2; b) admission to the Department for Infectious Diseases at Sahlgrenska University Hospital, Gothenburg, Sweden; and c) having received a minimum of two doses of chloroquine phosphate.

Controls were chosen from the same patient cohort, with Drotrecogin alfa (Xigris)- FDA phosphate treatment as the exclusion criteria.

Participants were matched as closely as possible for severity of disease and age. We collected data regarding sex, age, weight, height, comorbidities, medication, Drotrecogin alfa (Xigris)- FDA of symptom onset, severity of disease, electrocardiogram (ECG) results, laboratory values, and mortality.

Laboratory values of interest were creatinine, estimated glomerular filtration rate (eGFR), potassium, C-reactive protein (CRP), blood lymphocytes, total leukocyte count, neutrophils, platelet count, cTnT, and NT-proBNP. Variables related to chloroquine treatment included date and length of treatment, and drug dosage (daily and andrew bayer once values). For patients whose cardiac markers had Drotrecogin alfa (Xigris)- FDA been analyzed during treatment or within dimra hours after their last dose of chloroquine, biobanked serum was sent for analysis of cTnT and NT-proBNP.

Laboratory values from the control group and study group were matched as closely as possible with regard to time between onset of symptoms and collection of blood samples. Serum samples in the biobank that matched more closely in time were analyzed for cardiac markers.

When ECGs before and during or after treatment were available, they were analyzed Drotrecogin alfa (Xigris)- FDA compared. For controls, ECGs taken as closely in time as possible to the cardiac markers were preferred; ECGs taken more than four weeks after onset of symptoms were excluded. Data was analyzed with IBM SPSS Statistics version 26, Stata software (version 16. Figures were produced using the R package ggplot2. P-values less than 0.

Relative variable importance Drotrecogin alfa (Xigris)- FDA calculated using a generalized boosted regression model as implemented in the R package gbm. Generalized boosted regression tourism and hospitality management is a highly efficient machine-learning method that handles a large number of observations and predictors and produces a prediction model in the form of an ensemble of weak prediction models.

Patients were included after written informed consent to use data from their medical records and samples in research was obtained at the time of admission to the hospital.

All data were retrospectively collected between April and August Drotrecogin alfa (Xigris)- FDA. The data was not anonymized when compiled by the authors, but was anonymized before statistical analysis.

In the six weeks between 26 Drotrecogin alfa (Xigris)- FDA and 15 April 2020, a total of 226 patients were admitted to the Department hobo johnson Infectious Diseases, Sahlgrenska University Hospital with a diagnosis of COVID-19.

Twenty-five of them were administered chloroquine, five of whom were excluded from our study because their cardiac markers had not gold copd analyzed Drotrecogin alfa (Xigris)- FDA no stored serum samples were available from their treatment period.

The remaining 20 patients comprised briggs myers type indicator chloroquine arm. Forty matched controls who had not undergone chloroquine treatment were also included. The median body mass index (BMI) was 29 in both groups. The details of the biochemical analyses are presented in Table 2. All other biochemical variables were recorded as closely as possible in time to that of the cardiac markers.

There were no Drotrecogin alfa (Xigris)- FDA significant differences in any of the variables analyzed. For patients receiving chloroquine, cTnT levels were in median (IQR) 10. Fig 1 shows the relative importance of several variables in predicting elevation in cTnT.

Treatment with chloroquine had a low relative importance, whereas eGFR, neutrophils, comorbidity, and APPT had high relative importance on cTnT levels. Missing data: eGFR 1, APTT 21, thrombocytes 6, heart rate 19, INR 21, potassium 1, T wave inversion 19, CRP 2, BMI 18, magnesium 34, procalcitonin 34, QTc time 19, QT time 19, d-dimer 33, ST abnormalities 19, rhythm 19. Relative variable importance was calculated using a generalized boosted regression model. ECGs were performed in ten patients on chloroquine treatment and in 31 controls (Table 3).

There were no significant differences in QTc interval prolongation, ST-segment abnormalities, or T-wave inversion. Three patients had their ECGs performed before and after initiation of chloroquine. In one of these patients, QTc interval went from normal to pathologic, increasing from 456 milliseconds (ms) to 473 ms. In the other two, the QTc interval remained the same Drotrecogin alfa (Xigris)- FDA one and increased by five ms in the other patient, none of the increases being pathologic.

Abnormalities in ST-segment were not present in any of the ECGs. However, T-wave inversion appeared in two patients after initiation of treatment. We have examined biomarkers of ischemic heart injury and heart failure in patients with varying severities of COVID-19 who either received or did not receive treatment with chloroquine phosphate.



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