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Post-COVID Symptoms in Long-Haulers: Definition, Identification, Mechanisms, and Management

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Epidemiology & Public Health".

Deadline for manuscript submissions: closed (30 June 2022) | Viewed by 250285

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Prof. Dr. César Fernández-de-las-Peñas

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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

Prof. Dr. Domingo Palacios-Ceña

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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

Special Issue Information

Dear Colleagues,

SARS-CoV-2, the virus responsible for COVID-19, has spread rapidly across the world in the most unprecedent sanitary outbreak of this century. Current literature about COVID-19 has mainly concentrated on the disease itself and the management of acute cases. Today, the world is in front of a second pandemic associated with COVID-19, the “long-haulers”, individuals who recovered from COVID-19 but develop post-COVID-19 symptoms. The emerging literature supports the presence of several post-COVID-19 symptoms after the acute phase of COVID-19. However, several gaps exist in definitions, identification, timeframe, mechanisms, and treatment strategies for the management of post-COVID-19 symptoms. Better understanding of the underlying mechanisms behind post-COVID-19 symptoms and better identification of timeframes when these symptoms appear will help clinicians to improve future management of this new group of patients. This Special Issue will focus on all these aspects of post-COVID-19 symptomatology, a topic of emerging relevance due to the expected presence of millions of “long-haulers”. We invite researchers/clinicians to submit original articles, systematic reviews, narrative reviews, meta-analysis, case series, cohort, and case–control studies related to proper the identification and management of post-COVID-19 symptoms to this special issue.

Prof. Dr. César Fernández De Las Peñas
Prof. Dr. Domingo Palacios-Ceña
Guest Editors

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Keywords

COVID-19
symptoms
long-COVID
pain
function
fatigue
dyspnoea
public health

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Published Papers (7 papers)

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Editorial

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4 pages, 224 KiB

Open AccessEditorial

Special Issue “Post-COVID-19 Symptoms in Long-Haulers: Definition, Identification, Mechanisms, and Management”

by César Fernández-de-las-Peñas and Domingo Palacios-Ceña

J. Clin. Med. 2023, 12(20), 6458; https://doi.org/10.3390/jcm12206458 - 11 Oct 2023

Viewed by 1053

Abstract

The worldwide spread of coronavirus disease 2019 (COVID-19), a condition caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogen, led to the most unprecedented disease outbreak of this century, provoking around 770 million confirmed cases and nearly 7 million deaths globally [...] Read more.

(This article belongs to the Special Issue Post-COVID Symptoms in Long-Haulers: Definition, Identification, Mechanisms, and Management)

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13 pages, 1407 KiB

Open AccessArticle

Neuropsychological Predictors of Fatigue in Post-COVID Syndrome

by Jordi A. Matias-Guiu, Cristina Delgado-Alonso, María Díez-Cirarda, Álvaro Martínez-Petit, Silvia Oliver-Mas, Alfonso Delgado-Álvarez, Constanza Cuevas, María Valles-Salgado, María José Gil, Miguel Yus, Natividad Gómez-Ruiz, Carmen Polidura, Josué Pagán, Jorge Matías-Guiu and José Luis Ayala

J. Clin. Med. 2022, 11(13), 3886; https://doi.org/10.3390/jcm11133886 - 4 Jul 2022

Cited by 14 | Viewed by 3681

Abstract

Fatigue is one of the most disabling symptoms in several neurological disorders and has an important cognitive component. However, the relationship between self-reported cognitive fatigue and objective cognitive assessment results remains elusive. Patients with post-COVID syndrome often report fatigue and cognitive issues several months after the acute infection. We aimed to develop predictive models of fatigue using neuropsychological assessments to evaluate the relationship between cognitive fatigue and objective neuropsychological assessment results. We conducted a cross-sectional study of 113 patients with post-COVID syndrome, assessing them with the Modified Fatigue Impact Scale (MFIS) and a comprehensive neuropsychological battery including standardized and computerized cognitive tests. Several machine learning algorithms were developed to predict MFIS scores (total score and cognitive fatigue score) based on neuropsychological test scores. MFIS showed moderate correlations only with the Stroop Color–Word Interference Test. Classification models obtained modest F1-scores for classification between fatigue and non-fatigued or between 3 or 4 degrees of fatigue severity. Regression models to estimate the MFIS score did not achieve adequate R² metrics. Our study did not find reliable neuropsychological predictors of cognitive fatigue in the post-COVID syndrome. This has important implications for the interpretation of fatigue and cognitive assessment. Specifically, MFIS cognitive domain could not properly capture actual cognitive fatigue. In addition, our findings suggest different pathophysiological mechanisms of fatigue and cognitive dysfunction in post-COVID syndrome. Full article

(This article belongs to the Special Issue Post-COVID Symptoms in Long-Haulers: Definition, Identification, Mechanisms, and Management)

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11 pages, 764 KiB

Open AccessArticle

Detection of Male Hypogonadism in Patients with Post COVID-19 Condition

by Yukichika Yamamoto, Yuki Otsuka, Naruhiko Sunada, Kazuki Tokumasu, Yasuhiro Nakano, Hiroyuki Honda, Yasue Sakurada, Hideharu Hagiya, Yoshihisa Hanayama and Fumio Otsuka

J. Clin. Med. 2022, 11(7), 1955; https://doi.org/10.3390/jcm11071955 - 31 Mar 2022

Cited by 22 | Viewed by 3158

Abstract

The pathogenesis and prognosis of post COVID-19 condition have remained unclear. We set up an outpatient clinic specializing in long COVID in February 2021 and we have been investigating post COVID-19 condition. Based on the results of our earlier study showing that “general fatigue” mimicking myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is the most common symptom in long COVID patients, a retrospective analysis was performed for 39 male patients in whom serum free testosterone (FT) levels were measured out of 61 male patients who visited our clinic. We analyzed the medical records of the patients’ backgrounds, symptoms and laboratory results. Among the 39 patients, 19 patients (48.7%) met the criteria for late-onset hypogonadism (LOH; FT < 8.5 pg/mL: LOH group) and 14 patients were under 50 years of age. A weak negative correlation was found between age and serum FT level (r = −0.301, p = 0.0624). Symptoms including general fatigue, anxiety, cough and hair loss were more frequent in the LOH group than in the non-LOH group (FT ≥ 8.5 pg/mL). Among various laboratory parameters, blood hemoglobin level was slightly, but significantly, lower in the LOH group. Serum level of FT was positively correlated with the levels of blood hemoglobin and serum total protein and albumin in the total population, whereas these interrelationships were blurred in the LOH group. Collectively, the results indicate that the incidence of LOH is relatively high in male patients, even young male patients, with post COVID-19 and that serum FT measurement is useful for revealing occult LOH status in patients with long COVID. Full article

(This article belongs to the Special Issue Post-COVID Symptoms in Long-Haulers: Definition, Identification, Mechanisms, and Management)

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12 pages, 535 KiB

Open AccessArticle

Cardiopulmonary Exercise Performance and Endothelial Function in Convalescent COVID-19 Patients

by Pasquale Ambrosino, Paolo Parrella, Roberto Formisano, Giovanni Perrotta, Silvestro Ennio D’Anna, Marco Mosella, Antimo Papa and Mauro Maniscalco

J. Clin. Med. 2022, 11(5), 1452; https://doi.org/10.3390/jcm11051452 - 7 Mar 2022

Cited by 18 | Viewed by 3100

Abstract

Background: Endothelial dysfunction has been proposed as the common pathogenic background of most manifestations of coronavirus disease 2019 (COVID-19). Among these, some authors also reported an impaired exercise response during cardiopulmonary exercise testing (CPET). We aimed to explore the potential association between endothelial dysfunction and the reduced CPET performance in COVID-19 survivors. Methods: 36 consecutive COVID-19 survivors underwent symptom-limited incremental CPET and assessment of endothelium-dependent flow-mediate dilation (FMD) according to standardized protocols. Results: A significantly higher FMD was documented in patients with a preserved, as compared to those with a reduced, exercise capacity (4.11% ± 2.08 vs. 2.54% ± 1.85, p = 0.048), confirmed in a multivariate analysis (β = 0.899, p = 0.038). In the overall study population, FMD values showed a significant Pearson’s correlation with two primary CPET parameters, namely ventilation/carbon dioxide production (VE/VCO₂) slope (r = −0.371, p = 0.026) and end-tidal carbon dioxide tension (P_ETCO₂) at peak (r = 0.439, p = 0.007). In multiple linear regressions, FMD was the only independent predictor of VE/VCO₂ slope (β = −1.308, p = 0.029) and peak P_ETCO₂ values (β = 0.779, p = 0.021). Accordingly, when stratifying our study population based on their ventilatory efficiency, patients with a ventilatory class III-IV (VE/VCO₂ slope ≥ 36) exhibited significantly lower FMD values as compared to those with a ventilatory class I-II. Conclusions: The alteration of endothelial barrier properties in systemic and pulmonary circulation may represent a key pathogenic mechanism of the reduced CPET performance in COVID-19 survivors. Personalized pharmacological and rehabilitation strategies targeting endothelial function may represent an attractive therapeutic option. Full article

(This article belongs to the Special Issue Post-COVID Symptoms in Long-Haulers: Definition, Identification, Mechanisms, and Management)

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10 pages, 293 KiB

Open AccessArticle

Female Sex Is a Risk Factor Associated with Long-Term Post-COVID Related-Symptoms but Not with COVID-19 Symptoms: The LONG-COVID-EXP-CM Multicenter Study

by César Fernández-de-las-Peñas, José D. Martín-Guerrero, Óscar J. Pellicer-Valero, Esperanza Navarro-Pardo, Víctor Gómez-Mayordomo, María L. Cuadrado, José A. Arias-Navalón, Margarita Cigarán-Méndez, Valentín Hernández-Barrera and Lars Arendt-Nielsen

J. Clin. Med. 2022, 11(2), 413; https://doi.org/10.3390/jcm11020413 - 14 Jan 2022

Cited by 180 | Viewed by 229676

Abstract

This multicenter cohort study investigated the differences between coronavirus disease 2019 (COVID-19) related symptoms and post-COVID symptoms between male and female COVID-19 survivors. Clinical and hospitalization data were collected from hospital medical records in a sample of individuals recovered from COVID-19 at five public hospitals in Spain. A predefined list of post-COVID symptoms was systematically assessed, but patients were free to report any symptom. Anxiety/depressive levels and sleep quality were also assessed. Adjusted multivariate logistic regressions were used to identify the association of sex with post-COVID related-symptoms. A total of 1969 individuals (age: 61, SD: 16 years, 46.4% women) were assessed 8.4 months after discharge. No overall significant sex differences in COVID-19 onset symptoms at hospital admission were found. Post-COVID symptoms were present in up to 60% of hospitalized COVID-19 survivors eight months after the infection. The number of post-COVID symptoms was 2.25 for females and 1.5 for males. After adjusting by all variables, female sex was associated with ≥3 post-COVID symptoms (adj OR 2.54, 95%CI 1.671–3.865, p < 0.001), the presence of post-COVID fatigue (adj OR 1.514, 95%CI 1.040–2.205), dyspnea (rest: adj OR 1.428, 95%CI 1.081–1.886, exertion: adj OR 1.409, 95%CI 1.109–1.791), pain (adj OR 1.349, 95%CI 1.059–1.720), hair loss (adj OR 4.529, 95%CI 2.784–7.368), ocular problems (adj OR 1.981, 95%CI 1.185–3.312), depressive levels (adj OR 1.606, 95%CI 1.002–2.572) and worse sleep quality (adj OR 1.634, 95%CI 1.097–2.434). Female sex was a risk factor for the development of some long-term post-COVID symptoms including mood disorders. Healthcare systems should consider sex differences in the management of long haulers. Full article

(This article belongs to the Special Issue Post-COVID Symptoms in Long-Haulers: Definition, Identification, Mechanisms, and Management)

11 pages, 1318 KiB

Open AccessArticle

Post-COVID-19 Sydrome and Decrease in Health-Related Quality of Life in Kidney Transplant Recipients after SARS-COV-2 Infection—A Cohort Longitudinal Study from the North of Poland

by Agnieszka Malinowska, Marta Muchlado, Zuzanna Ślizień, Bogdan Biedunkiewicz, Zbigniew Heleniak, Alicja Dębska-Ślizień and Leszek Tylicki

J. Clin. Med. 2021, 10(21), 5205; https://doi.org/10.3390/jcm10215205 - 8 Nov 2021

Cited by 17 | Viewed by 2946

Abstract

Introduction: Patients after SARS-CoV-2 infection frequently face “Post-COVID-19 Syndrome”, defined by symptoms that develop during or after COVID-19, continue for more than 12 weeks, and are not explained by an alternative diagnosis. We aimed to evaluate the presence of post-COVID-19 syndrome and its predictors in kidney transplant recipients (KTR) 6 months after the disease. Materials and Methods: A total of 67 KTR (38 m) with a mean age of 53.6 ± 14 years, 7.3 ± 6.4 years post-transplant were included in the cohort longitudinal study. Thirty-nine (58.2%) of them were hospitalized, but not one required invasive ventilation therapy. They were interviewed 6 months after being infected, with a series of standardized questionnaires: a self-reported symptoms questionnaire, the modified British Medical Research Council (mMRC) dyspnea scale, EQ-5D-5L questionnaire, and EQ-VAS scale. Results: Post-COVID-19 syndrome was diagnosed in 70.1% of KTR and 26.9% of them reported at least three persistent symptoms. The most common symptoms were fatigue (43.3%), hair loss (31.3%), memory impairment (11.9%), muscle aches, and headaches (11.9%). Dyspnea with an mMRC scale grade of at least 1 was reported by 34.3% patients vs. 14.9% before infection; 47.8% stated that they still feel worse than before the disease. Mean EQ-VAS scores were 64.83 vs. 73.34 before infection. The persistent symptoms are more frequent in older patients and those with greater comorbidity. Conclusions: Persistent symptoms of post-COVID-19 syndrome are present in the majority of KTR, which highlights the need for long-term follow-up as well as diagnostic and rehabilitation programs. Full article

(This article belongs to the Special Issue Post-COVID Symptoms in Long-Haulers: Definition, Identification, Mechanisms, and Management)

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Review

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18 pages, 1498 KiB

Open AccessReview

Long COVID a New Derivative in the Chaos of SARS-CoV-2 Infection: The Emergent Pandemic?

by Diego Fernández-Lázaro, Nerea Sánchez-Serrano, Juan Mielgo-Ayuso, Juan Luis García-Hernández, Jerónimo J. González-Bernal and Jesús Seco-Calvo

J. Clin. Med. 2021, 10(24), 5799; https://doi.org/10.3390/jcm10245799 - 11 Dec 2021

Cited by 34 | Viewed by 5003

Abstract

Coronavirus disease 2019 (COVID-19) is a multisystem illness caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which can manifest with a multitude of symptoms in the setting of end-organ damage, though it is predominantly respiratory. However, various symptoms may remain after acute SARS-CoV-2 infection, and this condition is referred to as “Long COVID” (LC). Patients with LC may develop multi-organ symptom complex that remains 4–12 weeks after the acute phase of illness, with symptoms intermittently persisting over time. The main symptoms are fatigue, post-exertional malaise, cognitive dysfunction, and limitation of functional capacity. Pediatric patients developed the main symptoms of LC like those described in adults, although there may be variable presentations of LC in children. The underlying mechanisms of LC are not clearly known, although they may involve pathophysiological changes generated by virus persistence, immunological alterations secondary to virus–host interaction, tissue damage of inflammatory origin and hyperactivation of coagulation. Risk factors for developing LC would be female sex, more than five early symptoms, early dyspnea, previous psychiatric disorders, and alterations in immunological, inflammatory and coagulation parameters. There is currently no specific treatment for LC, but it could include pharmacological treatments to treat symptoms, supplements to restore nutritional, metabolic, and gut flora balance, and functional treatments for the most disabling symptoms. In summary, this study aims to show the scientific community the current knowledge of LC. Full article

(This article belongs to the Special Issue Post-COVID Symptoms in Long-Haulers: Definition, Identification, Mechanisms, and Management)

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