Inappropriate sinus tachycardia (IST) is a common observation in patients with post-COVID-19 syndrome (PCS) but has not yet been fully described to date. To investigate the prevalence and the mechanisms underlying IST in a prospective population of PCS patients. Consecutive patients admitted to the PCS Unit between June and December 2020 with a resting sinus rhythm rate ≥ 100 bpm were prospectively enrolled in this study and further examined by an orthostatic test, 2D echocardiography, 24-h ECG monitoring (heart rate variability was a surrogate for cardiac autonomic activity), quality-of-life and exercise capacity testing, and blood sampling. To assess cardiac autonomic function, a 2:1:1 comparative sub-analysis was conducted against both fully recovered patients with previous SARS-CoV-2 infection and individuals without prior SARS-CoV-2 infection. Among 200 PCS patients, 40 (20%) fulfilled the diagnostic criteria for IST (average age of 40.1 ± 10 years, 85% women, 83% mild COVID-19). No underlying structural heart disease, pro-inflammatory state, myocyte injury, or hypoxia were identified. IST was accompanied by a decrease in most heart rate variability parameters, especially those related to cardiovagal tone: pNN50 (cases 3.2 ± 3 vs. recovered 10.5 ± 8 vs. non-infected 17.3 ± 10; p < 0.001) and HF band (246 ± 179 vs. 463 ± 295 vs. 1048 ± 570, respectively; p < 0.001). IST is prevalent condition among PCS patients. Cardiac autonomic nervous system imbalance with decreased parasympathetic activity may explain this phenomenon.

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Funding Acknowledgements Type of funding sources: None. Background Persistent symptoms after the acute phase of SARS-CoV-2 infection are referred to as "post-COVID-19 syndrome" (PCS), with a reported incidence ranging between 35% and 87%. Fatigue, palpitations and exercise intolerance are common complains among PCS patients in whom unexplained sinus tachycardia, occasionally exacerbated by postural changes, is a frequent observation that remains poorly characterized. Purpose We sought to characterize the prevalence of inappropriate sinus tachycardia (IST) and postural orthostatic tachycardia (POTS) in a consecutive and prospective population of patients with PCS. Methods Consecutive patients with persistent symptoms 3 months after an acute SARS-CoV-2 infection were prospectively evaluated at a multi-disciplinary PCS unit. All patients were screened for IST or POTS and those with confirmed criteria underwent comprehensive cardiovascular examination including echocardiography, 24-hour Holter, Minnesota Living with Heart Failure Questionnaire (MLHFQ), six-minute walking test (6MWT) and inflammation and myocardial biomarkers. Two control patients, matched by age and gender, were assigned to each case: one with previous SARS-CoV-2 infection without PCS (group 2) and one without prior SARS-CoV-2 infection (group 3). Results IST or POTS criteria were met in 34 out of the 200 PCS patients (17%). The mean age was 39 ± 10 years, with 29 women (91%). The interval from the index COVID-19 disease to the PCS diagnosis was 71 ± 17 days, with a majority of patients (n = 29,85%) not requiring hospital admission during the acute phase. At physical examination, the mean heart rate was 96 ± 3bpm at supine and 112 ± 17bpm at the upright position, with 8 patients fulfilling diagnostic criteria of POTS. No underlying structural heart disease, pro-inflammatory state, myocyte injury or hypoxia were identified among our patient population. The 6MWT showed a significantly diminished exercise capacity with a 59% of the estimated distance after adjustment by age, sex and body mass index; an impaired quality of life was also identified, as suggested by a median MLFHQ total score of 67 out of 105 points. The 24-hour Holter showed an increase in HR predominantly during daytime in group 1 (mean daytime HR of 94 ± 3bpm), an altered heart rate variability with a decrease in time domain parameters [PNN50 4 ± 4 in group 1 (vs. 11 ± 9 in group 2 and 18 ± 9 in group 3; p &lt; 0.002)respectively; SD 100 ± 20 (vs. 127 ± 38 and 136 ± 13; p = 0.009) and a decrease in frequency domain parameters [LF 751 ± 450 (vs. 1721 ± 1009 and 2199 ± 920; p = 0.01), HF 336 ± 280 (vs. 823 ± 1200 and 1229 ± 630; p = 0.01)]. Conclusions IST and its POTS variant are a prevalent condition among PCS patients and may at least partially explain the common symptoms of fatigue, impaired exercise and palpitations that characterize the PCS. Cardiac autonomic nervous system imbalance may account as a plausible pathophysiological mechanism of IST in PCS patients.

ACTIV-3/TICO Study Group* Background: Ensovibep (MP0420) is a designed ankyrin repeat protein, a novel class of engineered proteins, under investigation as a treatment of SARS-CoV-2 infection.Objective: To investigate if ensovibep, in addition to remdesivir and other standard care, improves clinical outcomes among patients hospitalized with COVID-19 compared with standard care alone.

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