Evidence map›Paper›PMID 40692561›Full record

ArticleFrontiers in neurology2025

Comparative cohort study of post-acute COVID-19 infection with a nested, randomized controlled trial of ivabradine for those with postural orthostatic tachycardia syndrome (the COVIVA study).

David Saunders, Thomas B Arnold, Jason M Lavender, Daoqin Bi, Karl Alcover, Lydia D Hellwig, Sahar T Leazer, Roshila Mohammed, Bethelhem Markos, Kanchana Perera and 10 more

Registry-linked trialAbstract read
In one paragraph

Article in Frontiers in neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05481177 (Comparative Cohort Study of Post-acute COVID-19 Infection With a Nested, Randomized Controlled Trial of Ivabradine for Those With Postural Orthostatic Tachycardia Syndrome.), which is not on this map. Cited by 4 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT05481177 phase4unknown statusnot on this map

Comparative Cohort Study of Post-acute COVID-19 Infection With a Nested, Randomized Controlled Trial of Ivabradine for Those With Postural Orthostatic Tachycardia Syndrome.

TypeinterventionalSponsorUniformed Services University of the Health SciencesRan2023 to 2024Enrolled250ConditionsLong Haul COVID, Postural Orthostatic Tachycardia SyndromeArmsIvabradine
3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
  3. Review
  4. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

20 authors.

David SaundersUniformed Services University School of Medicine, Bethesda, MD, United States.
Thomas B ArnoldUniformed Services University School of Medicine, Bethesda, MD, United States.
Jason M LavenderUniformed Services University School of Medicine, Bethesda, MD, United States.
Daoqin BiUniformed Services University School of Medicine, Bethesda, MD, United States.
Karl AlcoverUniformed Services University School of Medicine, Bethesda, MD, United States.
Lydia D HellwigUniformed Services University School of Medicine, Bethesda, MD, United States.
Sahar T LeazerUniformed Services University School of Medicine, Bethesda, MD, United States.
Roshila MohammedUniformed Services University School of Medicine, Bethesda, MD, United States.
Bethelhem MarkosUniformed Services University School of Medicine, Bethesda, MD, United States.
Kanchana PereraUniformed Services University School of Medicine, Bethesda, MD, United States.
Dutchabong ShawUniformed Services University School of Medicine, Bethesda, MD, United States.
Priscilla KobiUniformed Services University School of Medicine, Bethesda, MD, United States.
Martin EvansWalter Reed Army Institute of Research, Silver Spring, MD, United States.
Autumn MainsUniformed Services University School of Medicine, Bethesda, MD, United States.
Marian Tanofsky-KraffUniformed Services University School of Medicine, Bethesda, MD, United States.
Emilie GoguetUniformed Services University School of Medicine, Bethesda, MD, United States.
Edward MitreUniformed Services University School of Medicine, Bethesda, MD, United States.
Kathleen P PrattUniformed Services University School of Medicine, Bethesda, MD, United States.
Clifton L DalgardUniformed Services University School of Medicine, Bethesda, MD, United States.
Mark C HaigneyUniformed Services University School of Medicine, Bethesda, MD, United States.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Significant clinical similarities have been observed between the recently described "Long-Haul" COVID-19 (LHC) syndrome, Postural Orthostatic Tachycardia Syndrome (POTS) and Inappropriate Sinus Tachycardia (IST). Shared symptoms include light-headedness, palpitations, tremulousness, generalized weakness, blurred vision, chest pain, dyspnea, "brain-fog," and fatigue. Ivabradine is a selective sinoatrial node blocker FDA-approved for management of tachycardia associated with stable angina and heart failure not fully managed by beta blockers. In our study we aim to identify risk factors underlying LHC, as well as the effectiveness of ivabradine in controlling heart rate dysregulations and POTS/IST related symptoms. Methods/design: A detailed prospective phenotypic evaluation combined with multi-omic analysis of 200 LHC volunteers will be conducted to identify risk factors for autonomic dysfunction. A comparator group of 50 volunteers with documented COVID-19 but without LHC will be enrolled to better understand the risk factors for LHC and autonomic dysfunction. Those in the cohort who meet diagnostic criteria for POTS or IST will be included in a nested prospective, randomized, placebo-controlled trial to assess the impact of ivabradine on symptoms and heart rate, assessed non-invasively based on physiologic response and ambulatory electrocardiogram. Additionally, studies on catecholamine production, mast cell and basophil degranulation, inflammatory biomarkers, and indicators of metabolic dysfunction will be measured to potentially provide molecular classification and mechanistic insights. Discussion: Optimal therapies for dysautonomia, particularly associated with LHC, have yet to be defined. In the present study, ivabradine, one of numerous proposed interventions, will be systematically evaluated for therapeutic potential in LHC-associated POTS and IST. Additionally, this study will further refine the characteristics of the LHC-associated POTS/IST phenotype, genotype and transcriptional profile, including immunologic and multi-omic analysis of persistent immune activation and dysregulation. The study will also explore and identify potential endotheliopathy and abnormalities of the clotting cascade. Clinical trial registration: https://clinicaltrials.gov/, identifier NCT05481177.

Indexed as

clinical trialivabradine (Procoralan)long-haul COVID-19postural orthostatic tachycardia syndromesevere acute respiratory syndrome coronavirus 2

Identifiers

PMID40692561
PMCPMC12278775

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.