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Open research questions in Long-Term Effects of COVID-19

994 gap statements mined from Long-Term Effects of COVID-19 papers in our 7.9M-paper local library, which holds 3,413 papers on the topic — drawn mostly from each paper's own stated research gap, future-work, challenge and limitation notes, and its abstract. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one.

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What the literature leaves open

  • The long-term clinical and radiological outcomes of OP-COVID-19 are not well understood. There is a need to identify factors associated with long-term fibrotic-like lesions in patients with OP-COVID-19.

    Clinical and Radiological Outcomes of Organising Pneumonia Secondary to COVID-19: A 2-Year Longitudinal Cohort Study · 2026 · DOI

  • There is a need to understand the prevalence and characteristics of post-infectious syndromes. The study aims to fill this gap by providing insights into post-infectious syndromes in the German general population.

    Post-infectious syndromes in the post-pandemic phase among the German general population · 2026 · DOI

  • Prior research has primarily focused on specific chronic conditions individually, rather than assessing the overall multimorbidity burden. The impact of COVID-19 on multimorbidity patterns among people with and without HIV is not well characterized.

    Increasing multimorbidity burden after COVID-19 Infection Among People with and without HIV in the United States: Insights from the National Clinical Cohort Collaborative (N3C) · 2026 · DOI

  • Functional outcomes and rehabilitation strategies were largely absent from recent reflections on the COVID-19 pandemic response and recovery. There is a need for effective rehabilitation programs for individuals hospitalized with COVID-19.

    REmotely monitored, Mobile health-supported Multidomain Rehabilitation with High Intensity Interval Training for COVID-19 (REMM-HIIT-CoV): Trial Design and Rationale · 2026 · DOI

  • Limited understanding of the specific pattern and extent of cognitive deficits in Post-COVID patients. Need for a better characterization of the cognitive impairments in Post-COVID patients. Lack of data on the prevalence of attentional and memory impairments in Post-COVID patients.

    Post-COVID: a specific neuropsychological profile in performance deficits · 2026 · DOI

  • Limited clinician education and clinical infrastructure for managing these conditions. Lack of systems-level support for patients with long COVID and other IACCs.

    Effectiveness of an Extension for Community Health Outcomes case-based virtual community of practice model on patient outcomes for the management of long COVID and other fatiguing illnesses: a randomized control trial · 2026 · DOI

  • The small EV sample size limited the use of secondary validation methods such as Western blot or flow cytometry. The study acknowledges the limitation of a single-subject analysis or a small sample size.

    Extracellular Vesicle Protein Cargo Reveals Potential Long-Term Biological Impact of Long COVID · 2026 · DOI

  • There is a need to identify the factors related to demographic variables and physical performance associated with quality of life in post-COVID-19 patients. Previous studies have reported that post-COVID-19 patients express decreased mobility and impaired ability to carry out daily activities, but the factors associated with these symptoms are not well understood.

    Factors Influencing Physical Performance and Quality of Life in Post-COVID-19 Patients · 2025 · DOI

  • There is a lack of quantitative analysis of the incidence of SIBO following COVID-19 infection. The study aims to address this gap by evaluating the prevalence and incidence of SIBO post-COVID-19 infection across different age groups.

    Progressive Increase in Small Intestinal Bacterial Overgrowth Risk Following COVID-19 Infection: A Global Population-Based Study · 2025 · DOI

  • Long COVID is still semi-unknown. There is a need to clarify some epidemiological, clinical, and laboratory characteristics of this disease.

    Severe Acute SARS-CoV-2 Infection and Long COVID: What Do We Know So Far? New Challenges in Diagnosis and Management · 2025 · DOI

  • The global prevalence of Long COVID is not precisely known. Long COVID represents a multisystem pathology lacking clear clinical boundaries and standardized patient management protocols. There is a need for an integrated approach that employs both personalized medicine and standardized protocols aimed at mitigating long-term consequences.

    Exploring the Pathophysiology of Long COVID: The Central Role of Low-Grade Inflammation and Multisystem Involvement · 2024 · DOI

  • The long-term effects of COVID-19 on the pulmonary vasculature are not well understood. The mechanisms of pulmonary vascular damage during acute infection are not fully elucidated. The role of thromboembolic events, endotheliitis, and hypoxic pulmonary vasoconstriction in COVID-19 is not fully understood.

    Mechanisms of Pulmonary Vasculopathy in Acute and Long-Term COVID-19: A Review · 2024 · DOI

  • Long COVID (LC) affects millions of people worldwide, yet its driving mechanisms remain incompletely defined and no treatment has been approved.

    Persistently activated virus-specific CD8 T cells indicate antigen-driven immune aberrations in long COVID · 2026 · DOI

  • Long COVID has been linked to persistent autonomic and vascular abnormalities, but its impact on hypertension among non‐hospitalized COVID‐19 convalescents remains unclear.

    Long‐COVID Associated With Incident Hypertension: A Population‐Based Cohort Study · 2026 · DOI

  • While the underlying mechanisms remain unclear, viral persistence and immune dysregulation are considered key contributors.

    Persistent Gut-Immune Axis dysregulation in long-term Post-COVID Syndrome: Insights from a prospective, observational, cross-sectional case-control study · 2026 · DOI

  • Asynchronous delivery appears feasible for general reconditioning, whereas its benefit for lower-limb strength and the value of synchronous supervision remain uncertain.

    Effects of Telerehabilitation on Quality of Life, Physical Capacity, and Symptom Burden Within the Post–COVID-19 Condition: Systematic Review and Meta-Analysis of Randomized Controlled Trials · 2026 · DOI

  • However, the effectiveness of telerehabilitation across clinical outcomes remains uncertain, and the influence of different delivery modes is not well understood.

    Effects of Telerehabilitation on Quality of Life, Physical Capacity, and Symptom Burden Within the Post–COVID-19 Condition: Systematic Review and Meta-Analysis of Randomized Controlled Trials · 2026 · DOI

  • Diet quality can be a potential modifier of post-acute COVID-19 syndrome (PACS), yet the relationship between dietary patterns, symptom burden, and biological markers remains poorly understood.

    Ultra-processed foods and diet quality in long COVID: associations with symptom burden, DNA damage, and inflammation · 2026 · DOI

  • However, little is known about how it impacts their daily lives and well-being from their own perspective.

    “It’s sad, and I want to go back to how things were before”: a qualitative study of young people’s experiences of living with long COVID · 2026 · DOI

  • Telemedical self-care approaches such as online Qigong and self-applied acupressure are increasingly used, yet little is known about how participants experience and integrate these interventions.

    Telemedical acupressure and Qigong for post-COVID fatigue: A qualitative study · 2026 · DOI

  • Yoga is a promising strategy that may help reduce post-COVID symptoms but remains understudied.

    Feasibility and preliminary effects of a yoga program developed for adults with post COVID-19 condition (Breathe Easy): Pilot randomized controlled trial · 2026 · DOI

  • Although gut microbiota changes have been reported in PCC and linked to PCC‐associated neurological manifestations, its relationship to structural or functional brain changes remains unexplored.

    Cross‐Sectional Associations Between Gut Microbiota and Neuroimaging Changes in Post‐ COVID ‐19 Condition · 2026 · DOI

  • Future research should investigate the causality of these findings and explore whether microbiome‐targeted therapeutic interventions might be associated with improvements in neurological symptoms and brain recovery.

    Cross‐Sectional Associations Between Gut Microbiota and Neuroimaging Changes in Post‐ COVID ‐19 Condition · 2026 · DOI

  • Small sample size of 25 outpatients, - Limited to non-hospitalized patients after mild COVID-19 infection, - No long-term follow-up data available, - Study design was prospective non-interventional, - Control selection was based on matching variables and was not informed by the present participants' physiological…

    Persistent exertional dyspnea following mild COVID-19: potential association with diaphragm impairment · 2026 · DOI

  • Further studies are needed to investigate the long-term effects of COVID-19 on respiratory muscle function, - Research should focus on the underlying mechanisms of diaphragm impairment in post-COVID-19 patients, - Studies should explore the potential benefits of targeted interventions to improve diaphragm function in patients with exertional dyspnea, - Investigation of the relationship between diaphragm impairment…

    Persistent exertional dyspnea following mild COVID-19: potential association with diaphragm impairment · 2026 · DOI

Most-cited papers in Long-Term Effects of COVID-19

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Open questions raised by papers listed on this page include: (1) The long-term clinical and radiological outcomes of OP-COVID-19 are not well understood (“Clinical and Radiological Outcomes of Organising Pneumonia Secondary to…”, 2026); (2) There is a need to understand the prevalence and characteristics of post-infectious syndromes (“Post-infectious syndromes in the post-pandemic phase among the German general…”, 2026); (3) The impact of COVID-19 on multimorbidity patterns among people with and without HIV is not well characterized (“Increasing multimorbidity burden after COVID-19 Infection Among People with and…”, 2026); (4) There is a need for effective rehabilitation programs for individuals hospitalized with COVID-19 (“REmotely monitored, Mobile health-supported Multidomain Rehabilitation with…”, 2026); (5) Lack of data on the prevalence of attentional and memory impairments in Post-COVID patients (“Post-COVID: a specific neuropsychological profile in performance deficits”, 2026). 994 gap statements have been mined from Long-Term Effects of COVID-19 papers in our 7.9M-paper local library, which holds 3,413 papers on the topic; the gaps come from whichever of those papers state one. They are mostly the research gaps the authors state and the papers' abstracts, plus future-work, limitations and challenges passages. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one, so you can read the original claim in context.

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