Electrocardiographic alterations in patients treated for acute Lassa Fever: Description of results from a phase II clinical trial in Nigeria

Background: Lassa virus (LASV) leads to high case fatality among hospitalized patients in West Africa. While the pathophysiology of the disease is poorly understood, cardiac pathology is suspected to constitute an important feature of severe Lassa Fever (LF). We report an analysis of electrocardiogram (ECG) findings of patients enrolled in a clinical trial comparing ribavirin with favipiravir for the treatment of LF. Methods: This randomized controlled open-label phase II clinical trial conducted at two reference hospitals for LF treatment in Nigeria, assessed the tolerability, safety and pharmacokinetics of favipiravir compared to ribavirin in the treatment of acute LF. Hospitalized adult participants with RT-PCR-confirmed mild LF were eligible to participate. Baseline and follow-up ECG readings were performed. Findings: From August 2021 to October 2022, 40 patients were included in the study (48 % female), and 36 completed the 10-day follow-up period. ECG alterations were similarly distributed between treatment arms and observed in 18 (45 %) participants, namely, T-wave inversion (n = 14; 35 %), conduction disorders (n = 5; 13 %), ST-segment elevation (n = 4; 10 %), and arrythmia (n = 2; 5 %). 36 % (n = 9) of the alterations observed subsided by the end of the study. Interpretation: ECG alterations observed in both treatment arms are compatible with direct cardiac effects of the LASV. The combination of new onset of chest pain combined with the evolution of ECG findings over time are suggestive for the occurrence of perimyocarditis in a subset of patients.