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Post-COVID Symptoms and Causes, 3rd Edition
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Post-COVID Symptoms and Causes, 3rd Edition

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Infectious Diseases".

Deadline for manuscript submissions: 31 May 2025 | Viewed by 4969

Special Issue Editors

Prof. Dr. Domingo Palacios-Ceña

E-Mail Website
Guest Editor
Department of Physical Therapy, Occupational Therapy, Rehabilitation and Physical Medicine, Universidad Rey Juan Carlos, 28922 Alcorcón, Madrid, Spain
Interests: qualitative research; mixed methods; caring science; vulnerable groups; disability and rehabilitation
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. César Fernández-de-las-Peñas

E-Mail Website
Guest Editor
Department of Physical Therapy, Occupational Therapy, Rehabilitation and Physical Medicine, Universidad Rey Juan Carlos, 28922 Alcorcón, Madrid, Spain
Interests: chronic pain; pain neuroscience education; manual therapy; central nervous system sensitization
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The SARS-CoV-2 infection has provoked an unprecedented worldwide crisis during the last years. Once the main outbreak has been controlled, clinicians and researchers are in front of a second crisis—the presence of long-lasting symptoms once the acute infection has been surpassed. An increasing number of studies and meta-analyses support the presence of more than 100 symptoms potentially attributed to COVID-19. There has been an advance in several aspects of this condition, called long-COVID or post-COVID-19, ranging from its definition, clinical diagnosis, and understanding of potential mechanisms to the identification of treatment strategies for its management. Due to the interest in the first two editions of this Special Issue, we are pleased to invite you to this Special Issue “Post-COVID Symptoms in Long-Haulers: Definition, Identification, Mechanisms and Management; 3rd Edition”.

Carrying on from the success of the first edition and second edition of the Special Issue “Post-COVID Symptoms and Causes”, this third edition of the Special Issue wants to continue providing knowledge on the mechanisms behind post COVID-19 conditions and the identification of subgroups of patients to improve the management strategies of these patients. This Special Issue Part III wants to further focus on aspects of post-COVID symptoms, a topic of emerging relevance due to the expected presence of millions of “long-haulers”. We invite researchers/clinicians to submit clinical trials, systematic reviews, narrative reviews, meta-analyses, cohort studies, or case–control studies related to the identification or management of post-COVID symptoms to this Special Issue. As with previous issues, the topic of the article can cover any post-COVID symptom, not being restricted to anyone. 

Prof. Dr. Domingo Palacios-Ceña
Prof. Dr. César Fernández-de-las-Peñas
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • COVID-19
  • symptoms
  • long-COVID
  • pain
  • function
  • fatigue
  • dyspnea
  • public health

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Related Special Issue

Published Papers (5 papers)

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Research

15 pages, 627 KiB  
Article
Physical Activity and Sedentary Behaviour in People with Long COVID: A Follow-Up from 12 to 18 Months After Discharge
by Nicola S. Diciolla, Ana Ampuero-López, Alda Marques, Ana Jiménez-Martín, Sara García-De Villa, María Torres-Lacomba and María José Yuste-Sánchez
J. Clin. Med. 2025, 14(11), 3641; https://doi.org/10.3390/jcm14113641 - 22 May 2025
Abstract
Background/Objectives: Long-term effects of post-COVID-19 on several health outcomes remain unclear. We assessed PA and sedentary behaviour changes and explored behaviour-change factors twelve months post-COVID-19 in people with and without Long COVID. Methods: A prospective cohort study followed people treated for [...] Read more.
Background/Objectives: Long-term effects of post-COVID-19 on several health outcomes remain unclear. We assessed PA and sedentary behaviour changes and explored behaviour-change factors twelve months post-COVID-19 in people with and without Long COVID. Methods: A prospective cohort study followed people treated for COVID-19 in different settings (home, hospital ward, intensive care unit) from twelve months to eighteen months post-COVID-19. Participants with and without Long COVID were identified. PA (Light PA-LPA, Moderate-to-Vigorous PA-MVPA, Steps·day−1), sedentary time, functional capacity (six-minute walk test-6MWT), muscle strength (quadriceps maximal voluntary contraction-QMVC), dyspnoea (modified Medical Research Council scale-mMRC), fatigue, symptoms of anxiety and depression, and health-related quality of life-HRQoL were assessed. Results: Among 148 participants (58 ± 15 years, 54% male), 101 had Long COVID. All remained physically inactive. People with Long COVID significantly increased LPA (LPALongCOVID +28 [1; 55] min·day−1; LPAControls +6 [−32; 45] min·day−1), and decreased MVPA (MVPALongCOVID −4 [−7; −2] min·day−1; MVPAControls −4 [−8; 1] min·day−1) and sedentarism (SedentarismLongCOVID −47 [−89; −4] min·day−1; SedentarismControls −30 [−88; 28] min·day−1). At eighteen months, higher proportions of individuals with Long COVID had impaired 6MWT (17% vs. 0%), reduced QMVC (25% vs. 6%), dyspnoea (24% vs. 0%), fatigue (67% vs. 13%), symptoms of anxiety (47% vs. 9%) and depression (26% vs. 0%) as well as poor HRQoL (50% vs. 6%). PA and sedentary behaviour changes at eighteen months were associated with dyspnoea and impaired QMVC at twelve months (LPA: mMRC ≥ 2: −41.56 [−129.30; 46.00] min·day−1, Steps·day−1: mMRC: −416.13 [−1223.83; 391.57]; QMVC ≤ 70% predicted: −1251.39 [−2661.69; 158.91], Sedentarism: mMRC ≥ 2: +47.21 [−90.57; 184.99] min·day−1; 0.24 ≤ R2 ≤ 0.32). Conclusions: PA and sedentary behaviour remain altered long after COVID-19, with people with Long COVID adjusting to fit lower PA levels, possibly driven by physical limitations and symptoms. Dyspnoea and muscle weakness may influence PA and sedentary behaviour. Full article
(This article belongs to the Special Issue Post-COVID Symptoms and Causes, 3rd Edition)
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10 pages, 921 KiB  
Article
Intravenous Administration of Remdesivir at the Acute Phase of SARS-CoV-2 Infection Is Associated with a Lower Prevalence of Post-COVID-19 Pain
by César Fernández-de-las-Peñas, Anabel Franco-Moreno, María Ruiz-Ruigómez, Estibaliz Arrieta-Ortubay, Pablo Ryan-Murua, Carlos Lumbreras-Bermejo, Pablo del-Valle-Loarte, Oscar J. Pellicer-Valero, Juan Torres-Macho, Rocco Giordano and Lars Arendt-Nielsen
J. Clin. Med. 2025, 14(9), 3156; https://doi.org/10.3390/jcm14093156 - 2 May 2025
Viewed by 288
Abstract
Background/Objective: Evidence suggests that the administration of antivirals at the acute phase of SARS-CoV-2 infection is associated with lower COVID-19 severity, accordingly, the administration of antivirals at the acute phase of the infection could prevent post-COVID-19 symptoms. The current study investigated the effects [...] Read more.
Background/Objective: Evidence suggests that the administration of antivirals at the acute phase of SARS-CoV-2 infection is associated with lower COVID-19 severity, accordingly, the administration of antivirals at the acute phase of the infection could prevent post-COVID-19 symptoms. The current study investigated the effects of the intravenous administration of Remdesivir at hospitalization (acute phase of SARS-CoV-2 infection) in COVID-19 survivors on the development of post-COVID-19 pain symptoms. Methods: A cohort of previously hospitalized COVID-19 survivors who received intravenous administration of Remdesivir at the acute COVID-19 phase (n = 216) were matched with a cohort of previously hospitalized COVID-19 survivors who did not receive any antiviral treatment at the acute phase of the infection (n = 216). In a face-to-face interview, they were asked for the development of pain symptoms attributed to SARS-CoV-2 infection and whether the symptom persisted at the time of the study (mean follow-up: 18.4, SD: 0.8 months). Clinical/hospitalization data were collected from medical records. Anxiety/depressive symptoms and sleep quality were also assessed with validated self-reported questionnaires. Results: No differences in hospitalization data and the presence of previous chronic conditions were seen between patients receiving or not receiving intravenous administration of Remdesivir during hospitalization. The multivariate analysis revealed that the intravenous administration of Remdesivir at the acute COVID-19 phase was a protective factor for the development of overall post-COVID-19 pain (OR 0.444, 95% CI 0.292–0.674, p < 0.001). A protective effect of administrating intravenous Remdesivir was specifically seen for thorax/chest (OR 0.277, 95% CI 0.100–0.766, p = 0.01) and lumbar spine (OR 0.347, 95% CI 0.143–0.844, p = 0.02) pain. Conclusions: Current results support a potential protective role of the intravenous administration of Remdesivir at the acute phase of SARS-CoV-2 infection for developing long-term post-COVID-19 pain in previously hospitalized COVID-19 survivors. Studies investigating the effects of the oral administration of antivirals in non-hospitalized populations are needed to generalize these findings. Full article
(This article belongs to the Special Issue Post-COVID Symptoms and Causes, 3rd Edition)
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13 pages, 2291 KiB  
Article
Long COVID in ARDS Survivors: Insights from a Two-Year-Follow-Up Study After the First Wave of the Pandemic
by Judit Aranda, Isabel Oriol, Núria Vázquez, Karim Ramos, Romina Concepción Suárez, Lucía Feria, Judith Peñafiel, Ana Coloma, Beatriz Borjabad, Raquel Clivillé, Montserrat Vacas and Jordi Carratalà
J. Clin. Med. 2025, 14(6), 1852; https://doi.org/10.3390/jcm14061852 - 10 Mar 2025
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Abstract
Objectives: To compare the health status, exercise capacity, and health-related quality of life (HRQoL) in survivors of COVID-19-associated acute respiratory distress syndrome (ARDS) at 8, 12, and 24 months post-diagnosis. Methods: We conducted a prospective, single-center follow-up study embedded within a larger multicenter [...] Read more.
Objectives: To compare the health status, exercise capacity, and health-related quality of life (HRQoL) in survivors of COVID-19-associated acute respiratory distress syndrome (ARDS) at 8, 12, and 24 months post-diagnosis. Methods: We conducted a prospective, single-center follow-up study embedded within a larger multicenter cohort of adults with COVID-19 who required hospital admission. Eligible participants underwent clinical interviews, physical examinations, chest radiography, and the 6-min walk test (6MWT). Standardized scales were used to assess post-traumatic stress disorder (PTSD), anxiety, depression, and HRQoL. Results: Out of 1295 patients with COVID-19, 365 developed ARDS, of whom 166 survived. After excluding deaths and loss to follow-up, 95 patients were monitored for 24 months. Over 60% of patients had persistent symptoms, though significant improvements were recorded in quality of life and physical recovery. More than 70% recovered their previous physical capacity, but 15% did not return to their usual lifestyle habits. Symptoms such as arthralgia and fatigue decreased, but cognitive issues, such as memory loss and insomnia, persisted. Radiological improvements were noted, although pulmonary function remained impaired. The prevalence of PTSD and anxiety decreased, while depression remained stable at around 30%. Conclusions: Long COVID continues to impose significant physical, mental, and social challenges. Symptoms like fatigue and anxiety have a profound impact on daily life. Strategies are urgently needed to help patients regain health and resume their normal lives. Full article
(This article belongs to the Special Issue Post-COVID Symptoms and Causes, 3rd Edition)
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16 pages, 712 KiB  
Article
Differential Fatigue Profile in Patients with Post-COVID Condition, Fibromyalgia, and Multiple Sclerosis
by Silvia Oliver-Mas, Jordi A. Matias-Guiu, Cristina Delgado-Alonso, Constanza Cuevas, José Manuel Alcalá Ramírez del Puerto, Juan Ignacio López-Carbonero, Jorge Matias-Guiu and Maria Diez-Cirarda
J. Clin. Med. 2025, 14(3), 952; https://doi.org/10.3390/jcm14030952 - 2 Feb 2025
Viewed by 2456
Abstract
Background/Objectives: Fatigue is a prevalent and debilitating symptom in Post-COVID Condition (PCC), fibromyalgia, and multiple sclerosis (MS). Although these conditions share clinical similarities, the underlying mechanisms of fatigue across these conditions may differ and remain poorly understood. This study aimed to compare the [...] Read more.
Background/Objectives: Fatigue is a prevalent and debilitating symptom in Post-COVID Condition (PCC), fibromyalgia, and multiple sclerosis (MS). Although these conditions share clinical similarities, the underlying mechanisms of fatigue across these conditions may differ and remain poorly understood. This study aimed to compare the intensity and characteristics of fatigue in these three conditions to identify shared and distinct features. Methods: We conducted a cross-sectional study involving 429 participants: 219 with PCC, 112 with fibromyalgia, and 98 with MS. Participants completed a questionnaire specifically developed for the study via the Google Forms platform. This questionnaire was developed by a group of professionals in the hospital specializing in fatigue related to these three conditions, in collaboration with expert patients. The questionnaire was reported following the Checklist for Reporting Results of Internet E-Surveys (CHERRIES) recommendations. Results: Fatigue intensity was significantly higher in PCC and fibromyalgia compared to MS. Some differences in fatigue characteristics were observed: MS patients reported more fatigue in response to heat and a greater impact of mood on fatigue. Furthermore, delayed fatigue and reduced benefits from rest were more pronounced in both PCC and fibromyalgia. No significant differences were found regarding cognitive fatigue or difficulties in predicting the ability to perform activities. Conclusions: These results underscore some clinical characteristics in the intensity and quality of fatigue across PCC, fibromyalgia, and MS. These findings could suggest different mechanisms in the pathophysiology of the fatigue. Our study underscores the need for tailored diagnostic tools and interventions in managing fatigue in these three conditions. Full article
(This article belongs to the Special Issue Post-COVID Symptoms and Causes, 3rd Edition)
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15 pages, 2559 KiB  
Article
A First Randomized Eight-Week Multidisciplinary Telerehabilitation Study for the Post-COVID-19 Condition: Improvements in Health- and Pain-Related Parameters
by Indre Bileviciute-Ljungar, Agneta Apelman, Lena Braconier, Sara Östhols, Jan-Rickard Norrefalk and Kristian Borg
J. Clin. Med. 2025, 14(2), 486; https://doi.org/10.3390/jcm14020486 - 14 Jan 2025
Viewed by 926
Abstract
Background/Objectives: This study investigates the effects of multidisciplinary telerehabilitation for the post-COVID-19 condition. Methods: Recruitment was announced during 2021/22 through the COVID patient organisation in Sweden. The key inclusion criteria were persistent symptoms and functional impairments longer than 12 weeks after an [...] Read more.
Background/Objectives: This study investigates the effects of multidisciplinary telerehabilitation for the post-COVID-19 condition. Methods: Recruitment was announced during 2021/22 through the COVID patient organisation in Sweden. The key inclusion criteria were persistent symptoms and functional impairments longer than 12 weeks after an acute SARS-CoV-2 infection, a stable health condition, and satisfactory skills to use the Internet. Participants were randomised into a rehabilitation group or a waiting list. Telerehabilitation was performed by a multidisciplinary team. Measured outcomes included health- and pain-related parameters and pain-related disability after eight weeks and when followed up after six months. Results: In total, 164 participants registered for the study. Of them, 67 participated in an eight-week group telerehabilitation programme (mean age 43, 78% women) and 42 stayed on a waiting list (mean age 47, 88% women) after eight weeks. Sixty participants from the rehabilitation group and 21 from the waiting list completed the data at the six-month follow-up. The results show greater improvements in both health- and pain-related parameters within the telerehabilitation group after eight weeks and six months than within the waiting list group (Cohen’s d effect size varied between moderate and large). However, no statistically significant differences were found between the groups, except participants being at a lower risk of anxiety measured based on the Hospital Anxiety and Depression Scale after eight weeks of telerehabilitation compared to those on the waiting list. Conclusions: The results indicate that multidisciplinary group telerehabilitation is beneficial for improving health- and pain-related parameters in people suffering from the post-COVID-19 condition and should be further developed and adapted for similar conditions, such as chronic pain, fatigue, etc. Full article
(This article belongs to the Special Issue Post-COVID Symptoms and Causes, 3rd Edition)
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