Journal of Clinical Medicine

Research

11 pages, 600 KiB

Open AccessArticle

Impaired Cardiovascular Hemodynamics in Patients Hospitalized with COVID-19 Pneumonia

by Barbara Domino, Agnieszka Włochacz, Małgorzata Maciorowska, Krzysztof Kłos, Andrzej Chciałowski, Małgorzata Banak, Beata Uziębło-Życzkowska and Paweł Krzesiński

J. Clin. Med. 2025, 14(6), 1806; https://doi.org/10.3390/jcm14061806 - 7 Mar 2025

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Abstract

Background: SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection may be associated with impaired cardiac function, especially in severe cases requiring hospitalization. Impedance cardiography (ICG) is a noninvasive method for assessing cardiac function. It could be useful for the early detection of hemodynamic [...] Read more.

Background: SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection may be associated with impaired cardiac function, especially in severe cases requiring hospitalization. Impedance cardiography (ICG) is a noninvasive method for assessing cardiac function. It could be useful for the early detection of hemodynamic dysfunction, particularly in patients with a severe course of COVID-19. Aim: This study aimed to analyze and compare the hemodynamic profiles of patients hospitalized with SARS-CoV-2-induced pneumonia to those of a control group. Methods: This prospective, observational, clinical study included 30 hospitalized patients (both men and women, mean age: 48 years) diagnosed with COVID-19 pneumonia (COVID group). Their data were compared to those of a retrospective control group (CG). The study participants were propensity score-matched based on clinical characteristics, including age, blood pressure (BP), and body mass index (BMI). ICG measurements of hemodynamic profiles were performed using a Niccomo device and included heart rate (HR), stroke volume index (SI), cardiac index (CI), velocity index (VI), acceleration index (ACI), Heather index (HI), systemic vascular resistance index (SVRI), and thoracic fluid content (TFC). Results: Patients with COVID-19 showed significantly higher HR (p < 0.0001) and SVRI (p = 0.0003) and lower values for several cardiac function parameters, including SI (p < 0.0001), VI (p < 0.0001), ACI (p = 0.004), and HI (p < 0.0001). Additionally, 11 patients (37%) in the COVID group had a low SI (<35 mL/m²), compared to only 1 patient (3%) in the control group (p < 0.0001). A statistically significant difference in left ventricular ejection fraction (LVEF) was also observed (p < 0.0001), although absolute values remained within the normal range. Conclusions: SARS-CoV-2 infection negatively affects the cardiovascular system, leading to impaired heart function even in low-risk patients. Impedance cardiography may serve as a simple, noninvasive tool for identifying individuals with cardiac dysfunction following COVID-19 pneumonia. Full article

(This article belongs to the Special Issue Novel Insights into COVID-19-Associated Complications and Sequelae)

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13 pages, 1704 KiB

Open AccessArticle

Broad-Spectrum Adverse Events of Special Interests Based on Immune Response Following COVID-19 Vaccination: A Large-Scale Population-Based Cohort Study

by Hong Jin Kim, Jee Hyun Suh, Min-Ho Kim, Myeong Geun Choi and Eun Mi Chun

J. Clin. Med. 2025, 14(5), 1767; https://doi.org/10.3390/jcm14051767 - 6 Mar 2025

Viewed by 11881

Abstract

Background/Objectives: Current studies on adverse events related to the COVID-19 vaccine have predominantly focused on severe, life-threatening side effects. However, numerous less severe but common adverse events (AEs) remain underreported and insufficiently investigated despite their potential impact. Methods: This population-based cohort study investigated [...] Read more.

Background/Objectives: Current studies on adverse events related to the COVID-19 vaccine have predominantly focused on severe, life-threatening side effects. However, numerous less severe but common adverse events (AEs) remain underreported and insufficiently investigated despite their potential impact. Methods: This population-based cohort study investigated the cumulative incidence rate (cIR) and risk of the broad-spectrum AEs of special interests (AESIs) based on immune response, including gynecological, dermatological, ophthalmological, otologic, and dental problems, following COVID-19 vaccination. Results: Among 4,203,887 individuals in Seoul, South Korea, the final analysis included 1,458,557 vaccinated subjects and 289,579 non-vaccinated subjects after the exclusion of underlying diseases. The cIR of AESIs for three months was significantly higher in vaccinated subjects than in non-vaccinated subjects, except for endometriosis. The vaccination significantly increased the risks of all the AESIs except for visual impairment. The risk of alopecia showed the highest HRs (HR [95% CI] = 2.40 [1.90–3.03]) among the AESIs following COVID-19 vaccination. Among the vaccinated subjects, heterologous vaccination was associated with the increased risk of most of the AESIs. Conclusions: Our findings suggest that clinicians should closely recognize and follow up on various COVID-19 vaccine-related AEs due to their unknown impact, even if they may not be serious at present. Full article

(This article belongs to the Special Issue Novel Insights into COVID-19-Associated Complications and Sequelae)

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17 pages, 472 KiB

Open AccessArticle

Three-Year Follow-Up of COVID-19 Cases in District of Constance, Germany. A Prospective, Controlled Cohort Study (FSC19-KN)

by Ann-Kathrin Kohler, Stephan Richter, Michael Schmid, Heidi Zimmermann, Hannes Winterer, Steffen Schneider and Marc Kollum

J. Clin. Med. 2025, 14(5), 1439; https://doi.org/10.3390/jcm14051439 - 21 Feb 2025

Viewed by 490

Abstract

Background and Objectives: Long-term sequalae of viral diseases, especially after infections with SARS-CoV-2 (COVID-19), can induce multi-organ involvement, as around 65 million people worldwide report persistent symptoms that go far beyond the acute course. Studies indicate that early virus variants pose a [...] Read more.

Background and Objectives: Long-term sequalae of viral diseases, especially after infections with SARS-CoV-2 (COVID-19), can induce multi-organ involvement, as around 65 million people worldwide report persistent symptoms that go far beyond the acute course. Studies indicate that early virus variants pose a higher risk of developing post-COVID-19 conditions. The primary aim of this study was to investigate the possible long-term effects based on the hospitalization rates and associated clinical events in patients infected with SARS-CoV-2 over an observational period of three years after the initial infection. Secondarily, an investigation of health-related quality of life and functional status was performed. Methods and Materials: The study presented was designed as a prospective, controlled cohort study to follow up on COVID-19 cases in the district of Konstanz, Germany (FSC19-KN). The positive group included subjects who had a primary infection with SARS-CoV-2 between March and December 2020. The control group included subjects who did not have a SARS-CoV-2 infection, as evidenced by a negative antibody test. As the primary endpoint, hospitalization rates and respective related admission diagnosis during the observational period of three years from January 2021 until July 2024 were analyzed. The health-related quality of life and functional outcomes were measured by the SF-36 questionnaire and Post-COVID-19 Functional Status (PCFS) as the secondary endpoint. Results: During the three years of observation after inclusion in the study, the hospitalization rate did not differ significantly between the two groups of initially infected and non-infected subjects (cumulative events, verum group 57 to control group 45, OR 1.24, CI 0.83; 1.85, p = 0.30). However, the health-related quality of life, measured by SF-36 sub scores of the SARS-CoV-2-positive subjects, achieved significantly lower results, except for the dimension ‘energy and fatigue’, in which subjects of the verum group still achieved significantly lower scores. Conclusions: Mild COVID-19 cases have no significant impact on hospitalization rates during an observational period of three years after initial infection. Yet, SARS-CoV-2-positive subjects reported a reduced health-related quality of life and functional outcomes. Ultimately, only the sub score quality ‘energy and fatigue’ still registered significant differences between both cohorts at the end of the three-year observational period. Full article

(This article belongs to the Special Issue Novel Insights into COVID-19-Associated Complications and Sequelae)

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11 pages, 571 KiB

Open AccessArticle

Course of General Fatigue in Patients with Post-COVID-19 Conditions Who Were Prescribed Hochuekkito: A Single-Center Exploratory Pilot Study

by Kazuki Tokumasu, Nobuyoshi Matsuki, Yuki Otsuka, Yoko Sakamoto, Keigo Ueda, Yui Matsuda, Yasue Sakurada, Hiroyuki Honda, Yasuhiro Nakano, Toru Hasegawa, Ryosuke Takase, Daisuke Omura and Fumio Otsuka

J. Clin. Med. 2025, 14(4), 1391; https://doi.org/10.3390/jcm14041391 - 19 Feb 2025

Viewed by 797

Abstract

Background: After the start of the COVID-19 pandemic, general fatigue in patients with long COVID and post-COVID-19 conditions (PCC) became a medical issue. Although there is a lack of evidence-based treatments, Kampo medicine (traditional Japanese medicine) has gained attention in Japan. At [...] Read more.

Background: After the start of the COVID-19 pandemic, general fatigue in patients with long COVID and post-COVID-19 conditions (PCC) became a medical issue. Although there is a lack of evidence-based treatments, Kampo medicine (traditional Japanese medicine) has gained attention in Japan. At an outpatient clinic in Japan specializing in long COVID, 24% of all prescriptions were Kampo medicines, and 72% of Kampo medicine prescriptions were hochuekkito. However, there has been no prospective, quantitative study on the course of fatigue in patients with long COVID and PCC who were prescribed hochuekkito. The aim of this study was to clarify the course of fatigue in those patients. Methods: This study included patients aged 18 years or older with general fatigue who visited the long COVID specialized outpatient clinic at Okayama University Hospital and consented to participate after being prescribed hochuekkito. We reviewed the backgrounds of the patients, and we evaluated the patients’ fatigue assessment scale in person or online. Results: Twenty patients were enrolled in this study from September to December in 2023. The average age of the patients was 42.9 years (SD: 15.8 years) and 12 patients (60%) were female. After hochuekkito administration, the fatigue assessment scale score decreased from 35.9 (SD: 5.9) at the initial visit to 31.2 (SD: 9.4) after 8 weeks, indicating a trend for improvement in fatigue (difference: 4.7; 95% CI: 0.5–8.9). Conclusions: A trend for improvement in fatigue was observed in patients with long COVID and PCC who were prescribed hochuekkito, indicating a potential benefit of hochuekkito for general fatigue in such patients. General fatigue in patients with long COVID or PCC can be classified as post-infectious fatigue syndrome and is considered a condition of qi deficiency in Kampo medicine, for which hochuekkito is appropriately indicated. Full article

(This article belongs to the Special Issue Novel Insights into COVID-19-Associated Complications and Sequelae)

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10 pages, 680 KiB

Open AccessArticle

The Tinetti Balance Test Is an Effective Predictor of Functional Decline in Non-Hospitalized Post-COVID-19 Individuals: A Cross-Sectional Study

by Janice R. M. Bastos, Arthur S. Ferreira, Agnaldo J. Lopes, Talita P. Pinto, Erika Rodrigues and Fabio V. dos Anjos

J. Clin. Med. 2024, 13(21), 6626; https://doi.org/10.3390/jcm13216626 - 4 Nov 2024

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Abstract

Background/Objectives: Individuals with post-COVID-19 conditions risk developing short- and/or long-term neuromuscular impairments, including postural imbalance. However, there is limited evidence showing whether balance deficits are associated with declines in the functional status in post-COVID-19 individuals. This study examined postural balance in non-hospitalized post-COVID-19 [...] Read more.

Background/Objectives: Individuals with post-COVID-19 conditions risk developing short- and/or long-term neuromuscular impairments, including postural imbalance. However, there is limited evidence showing whether balance deficits are associated with declines in the functional status in post-COVID-19 individuals. This study examined postural balance in non-hospitalized post-COVID-19 individuals using different assessment tools and tested the most relevant balance tools in predicting functional status. Methods: This cross-sectional study enrolled 60 adults split into control (n = 30) and post-COVID-19 (n = 30) groups. Postural balance was assessed in both groups using the Functional Reach Test (FRT), Berg Balance Scale (BBS), Timed Up and Go (TUG), Tinetti Balance Test (Tinetti), and Mini-BESTest (MBT). Functional status in the post-COVID-19 group was assessed using post-COVID-19 functional status (PCFS). Results: Significant differences in postural stability between groups were found only for the FRT. All balance tests showed a statistically significant correlation with PCFS in the post-COVID-19 group, with better performance in all tests being associated with better functional status: Tinetti (r = −0.584), FRT (r = −0.542), MBT (r = −0.530), BBS (r = −0.415) and TUG (r = 0.368). Tinetti was the independent variable that significantly played an important role in determining PCFS (adjusted R² = 0.318, p < 0.001). Conclusions: Post-COVID-19 functional status is best determined by the Tinetti Balance Test, making it an effective tool for assessing postural balance deficits in this population, with potential implications for postural control assessment and rehabilitation. Full article

(This article belongs to the Special Issue Novel Insights into COVID-19-Associated Complications and Sequelae)

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21 pages, 2312 KiB

Open AccessArticle

Impact of Comorbidities and Skin Diseases on Post-Vaccination Reactions: A Study on COVID-19 Vaccinations in Poland

by Izabela Jęśkowiak-Kossakowska, Paulina Nowotarska, Patrycja Grosman-Dziewiszek, Adam Szeląg and Benita Wiatrak

J. Clin. Med. 2024, 13(20), 6173; https://doi.org/10.3390/jcm13206173 - 17 Oct 2024

Viewed by 1611

Abstract

Background: The COVID-19 pandemic necessitated rapid and widespread vaccination efforts, which proved critical in reducing the severity and mortality of the virus. However, the interplay between vaccinations, pre-existing skin conditions, and other comorbidities still needs to be explored. This study investigated the occurrence [...] Read more.

Background: The COVID-19 pandemic necessitated rapid and widespread vaccination efforts, which proved critical in reducing the severity and mortality of the virus. However, the interplay between vaccinations, pre-existing skin conditions, and other comorbidities still needs to be explored. This study investigated the occurrence and severity of adverse events following immunization (AEFIs) with COVID-19 vaccines in individuals with chronic skin diseases and comorbidities within a Central European cohort. Methods: An anonymous online survey was conducted between May 2022 and February 2023, targeting students and employees of universities in Wrocław, Poland. A total of 513 respondents were analyzed, focusing on AEFIs following the first, second, and third doses of COVID-19 vaccines and the effects of COVID-19 on conditions such as atopic dermatitis, psoriasis, vitiligo, acne vulgaris, rosacea, and various comorbidities. Results: COVID-19 vaccination effectively protected against severe disease across all doses. The analysis revealed no significant impact of either COVID-19 infection or vaccination on the course of selected skin diseases and comorbidities. The reporting of AEFIs to the Sanitary Inspection was notably low. The Moderna and Pfizer mRNA-based vaccines were associated with a higher reported number of AEFIs, particularly after the second and third doses, compared to AstraZeneca, which exhibited fewer adverse events after subsequent doses. Conclusions: COVID-19 vaccination is both safe and effective, even in patients with pre-existing skin conditions and comorbidities. Vaccine selection may benefit from considering individual health profiles, and better reporting of AEFIs is needed to enhance vaccine safety monitoring. Full article

(This article belongs to the Special Issue Novel Insights into COVID-19-Associated Complications and Sequelae)

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13 pages, 666 KiB

Open AccessFeature PaperArticle

Outcomes and Healthcare Resource Utilization in Patients with COVID-19 Treated with Nirmatrelvir–Ritonavir: Real-World Data Analysis

by Clara Weil, Lilac Tene, Gabriel Chodick, Noga Fallach, Wajeeha Ansari, Tal Distelman-Menachem and Yasmin Maor

J. Clin. Med. 2024, 13(20), 6091; https://doi.org/10.3390/jcm13206091 - 12 Oct 2024

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Abstract

Background: Nirmatrelvir–ritonavir was granted emergency use authorization in Israel in January 2022 to treat high-risk patients with mild-to-moderate COVID-19. The aim of the study was to assess the association between nirmatrelvir–ritonavir treatment and COVID-19-related hospitalization and healthcare resource utilization (HCRU) in a country [...] Read more.

Background: Nirmatrelvir–ritonavir was granted emergency use authorization in Israel in January 2022 to treat high-risk patients with mild-to-moderate COVID-19. The aim of the study was to assess the association between nirmatrelvir–ritonavir treatment and COVID-19-related hospitalization and healthcare resource utilization (HCRU) in a country with a high level of vaccinations compared to patients who were offered treatment and declined. Methods: The Maccabi Healthcare Services dataset was used to identify high-risk SARS-CoV-2-positive adults from January to February 2022 who received nirmatrelvir–ritonavir within 5 days of symptom onset (treatment group) or who were offered nirmatrelvir–ritonavir treatment and declined it (reference group). COVID-19-related hospitalizations and all-cause mortality and HCRU within 30 days were compared between treatment and reference groups using inverse probability of treatment weighting. Results: Treatment and reference groups included 3460 (median age, 68.4 years) and 1654 (70.2 years) patients, respectively. Patients with ≥1 dose of COVID-19 vaccine accounted for 89.5% (treatment group) and 72.1% (reference group) of the total. Treatment was associated with a lower risk of COVID-19-related hospitalization (adjusted OR, 0.59 [95% CI, 0.41,0.83]). Results were similar by age group (18–64/≥65 years) and among patients with/without vaccination in the prior 180 days. There were 11 (0.3%) versus 11 (0.7%) deaths in the treatment and reference groups, respectively. Treated patients had lower inpatient HCRU and greater less intensive outpatient HCRU (e.g., telemedicine and emergency room visits). Conclusions: Nirmatrelvir–ritonavir treatment was associated with a reduced risk of COVID-19-related hospitalization and a shift to less intensive outpatient HCRU. Comparison with a reference group of nirmatrelvir–ritonavir-eligible patients who declined treatment enabled an unbiased outcome assessment. Real-world data gathered during the Omicron BA.1 variant wave of COVID-19 in Israel support the continued use of nirmatrelvir–ritonavir for high-risk adults of all ages, regardless of previous vaccinations. Full article

(This article belongs to the Special Issue Novel Insights into COVID-19-Associated Complications and Sequelae)

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18 pages, 4776 KiB

Open AccessArticle

Retinal Microvasculature Changes Linked to Executive Function Impairment after COVID-19

by Mar Ariza, Barbara Delas, Beatriz Rodriguez, Beatriz De Frutos, Neus Cano, Bàrbara Segura, Cristian Barrué, Javier Bejar, Mouafk Asaad, Claudio Ulises Cortés, Carme Junqué, Maite Garolera and NAUTILUS Project Collaborative Group

J. Clin. Med. 2024, 13(19), 5671; https://doi.org/10.3390/jcm13195671 - 24 Sep 2024

Viewed by 3100

Abstract

Background/Objectives: Studies using optical coherence tomography angiography (OCTA) have revealed that individuals recovering from COVID-19 have a reduced retinal vascular density (VD) and larger foveal avascular zones (FAZs) than healthy individuals, with more severe cases showing greater reductions. We aimed to examine [...] Read more.

Background/Objectives: Studies using optical coherence tomography angiography (OCTA) have revealed that individuals recovering from COVID-19 have a reduced retinal vascular density (VD) and larger foveal avascular zones (FAZs) than healthy individuals, with more severe cases showing greater reductions. We aimed to examine aspects of the retinal microvascularization in patients with post-COVID-19 condition (PCC) classified by COVID-19 severity and how these aspects relate to cognitive performance. Methods: This observational cross-sectional study included 104 PCC participants from the NAUTILUS Project, divided into severe (n = 59) and mild (n = 45) COVID-19 groups. Participants underwent cognitive assessments and OCTA to measure VD and perfusion density (PD) in the superficial capillary plexus (SVP) and FAZ. Analysis of covariance and partial Pearson and Spearman correlations were used to study intergroup differences and the relationships between cognitive and OCTA variables. Results: Severe PCC participants had significantly lower central (p = 0.03) and total (p = 0.03) VD, lower central (p = 0.02) PD measurements, and larger FAZ areas (p = 0.02) and perimeters (p = 0.02) than mild cases. Severe cases showed more cognitive impairment, particularly in speed processing (p = 0.003) and executive functions (p = 0.03). Lower central VD, lower central PD, and larger FAZ areas and perimeters were associated with worse executive function performance in the entire PCC sample and in the mild COVID-19 group. Conclusions: Retinal microvascular alterations, characterized by reduced VD and PD in the SVP and larger FAZ areas, were associated with cognitive impairments in PCC individuals. These findings suggest that severe COVID-19 leads to long-lasting microvascular damage, impacting retinal and cognitive health. Full article

(This article belongs to the Special Issue Novel Insights into COVID-19-Associated Complications and Sequelae)

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11 pages, 1572 KiB

Open AccessArticle

Importance of Blood Glucose Measurement for Predicting the Prognosis of Long COVID: A Retrospective Study in Japan

by Sho Yokoyama, Hiroyuki Honda, Yuki Otsuka, Kazuki Tokumasu, Yasuhiro Nakano, Yasue Sakurada, Yui Matsuda, Naruhiko Sunada, Toru Hasegawa, Ryosuke Takase, Daisuke Omura, Yoshiaki Soejima, Keigo Ueda, Masayuki Kishida and Fumio Otsuka

J. Clin. Med. 2024, 13(14), 4099; https://doi.org/10.3390/jcm13144099 - 13 Jul 2024

Cited by 1 | Viewed by 1604

Abstract

Purpose: The present study aimed to clarify the effects of a hyperglycemic condition on the clinical consequences of long COVID. Methods: Among 643 patients who visited the outpatient clinic of our hospital from February 2021 to September 2023, long COVID patients were classified [...] Read more.

Purpose: The present study aimed to clarify the effects of a hyperglycemic condition on the clinical consequences of long COVID. Methods: Among 643 patients who visited the outpatient clinic of our hospital from February 2021 to September 2023, long COVID patients were classified into a hyperglycemic (HG) group with casual blood glucose levels above 140 mg/dL and a normoglycemic (NG) group. The patients’ backgrounds, clinical symptoms, health status including the QOL evaluation scale (EQ-5D-5L), self-rating depression scale (SDS), and F-scale questionnaire (FSSG), blood test data, and recovery periods were analyzed. Results: The NG group included 607 patients with long COVID and the HG group included 36 patients with long COVID. Patients in the HG group were older than those in the NG group (55 vs. 41 years; p < 0.001) and included a larger percentage of males (67% vs. 44%; p = 0.009). The HG group had a larger percentage of patients with moderate-to-severe conditions in the acute infection phase (28% vs. 12%; p = 0.008), a higher BMI (25 vs. 22 kg/m²; p < 0.001), higher blood pressure (138/81 vs. 122/72 mmHg; p < 0.001), and a larger percentage of patients with an alcohol drinking habit (53% vs. 34%; p = 0.031). Long COVID symptoms and self-rated scales were not differed between the two groups; however, the laboratory data showed that liver and renal functions and metabolic data were significantly worse in the HG group. Although there was no apparent difference between the two groups in duration from the infection to the first visit, the HG group had a significantly longer period of recovery from long COVID (median period of 421 vs. 294 days; p = 0.019). Conclusion: A hyperglycemic state associated with other lifestyle-related diseases is associated with the prolongation of recovery from long COVID. Full article

(This article belongs to the Special Issue Novel Insights into COVID-19-Associated Complications and Sequelae)

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11 pages, 259 KiB

Open AccessArticle

Pericardial and Pleural Effusions in Non-ICU Hospitalized Patients with COVID-19—A Retrospective Single-Center Study

by David V. Mangaloiu, Cătălin Tilișcan, Alexandra D. Răriș, Anca R. Negru, Violeta Molagic, Constanta A. Vișan, Laurențiu M. Stratan, Nicoleta Mihai, Ștefan S. Aramă and Victoria Aramă

J. Clin. Med. 2024, 13(13), 3749; https://doi.org/10.3390/jcm13133749 - 27 Jun 2024

Viewed by 1580

Abstract

Background: Pericardial and pleural effusions are two complications recently described in patients hospitalized with COVID-19 infections. There are several mechanisms that have been proposed and refer to SARS-CoV-2’s capacity to bind to cell surfaces via various receptors and its broad tissue tropism [...] Read more.

Background: Pericardial and pleural effusions are two complications recently described in patients hospitalized with COVID-19 infections. There are several mechanisms that have been proposed and refer to SARS-CoV-2’s capacity to bind to cell surfaces via various receptors and its broad tissue tropism that might cause significant complications. The aim of the present study is to evaluate the incidence of pericardial and pleural effusions during COVID-19 infection as well as to determine the risk factors associated with these complications. Methods: We conducted a retrospective single-center study that included 346 patients admitted to the National Institute of Infectious Disease “Prof. Dr. Matei Bals” (Bucharest, Romania), from 1 January to 25 May 2021, during the third wave of the pandemic. Socio-demographic and anthropometric data were collected for each patient. The patients were evaluated clinically, biologically, and radiologically within 48 h of admission. Patients were divided into 3 groups: (1) patients with pericardial effusions—18; (2) patients with pleural effusions—28; (3) patients without pericardial/pleural effusions—294. Results: After exclusion criteria were applied, 337 patients were analyzed. The median age of the participants was 58.26 ± 14.58 years. More than half of the hospitalized patients had associated respiratory failure (61.5%), of which 2.7% had a critical form of the disease and 58.8% had a severe form. The cumulative percentage for pericardial and pleural effusions for the study group was 12.8% (43 patients out of 337). The prevalence of pericardial effusion was 5.3%, twice more frequent among male respondents. Pleural effusion was identified in 8.3% patients. Most patients had unilateral effusion (17), compared to 11 patients who had bilateral involvement. Based on laboratory results, patients with pericardial and pleural effusions exhibited increased levels of C reactive protein, erythrocyte sedimentation rate, NT proBNP, and a higher value of neutrophil/lymphocyte count ratio. In contrast to patients without pleural and pericardial effusions, those with these symptoms experienced a higher frequency of severe or critical illness and longer hospital stays. Conclusions: Pericardial and pleural effusions can complicate COVID-19 infections. In our study, the prevalence of pericardial and pleural effusions in hospitalized patients was low, being associated with the same comorbidities and a number of clinical and biological parameters. Full article

(This article belongs to the Special Issue Novel Insights into COVID-19-Associated Complications and Sequelae)

15 pages, 2475 KiB

Open AccessArticle

Tackling Post-COVID-19 Rehabilitation Challenges: A Pilot Clinical Trial Investigating the Role of Robotic-Assisted Hand Rehabilitation

by Ana Cisnal, Gonzalo Alonso-Linaje, Juan Carlos Fraile, Javier Pérez-Turiel, Pablo Álvarez and Socorro Martinez

J. Clin. Med. 2024, 13(6), 1543; https://doi.org/10.3390/jcm13061543 - 7 Mar 2024

Cited by 3 | Viewed by 1743

Abstract

Background: Prolonged hospitalization in severe COVID-19 cases can lead to substantial muscle loss and functional deterioration. While rehabilitation is essential, conventional approaches face capacity challenges. Therefore, evaluating the effectiveness of robotic-assisted rehabilitation for patients with post-COVID-19 fatigue syndrome to enhance both motor function [...] Read more.

Background: Prolonged hospitalization in severe COVID-19 cases can lead to substantial muscle loss and functional deterioration. While rehabilitation is essential, conventional approaches face capacity challenges. Therefore, evaluating the effectiveness of robotic-assisted rehabilitation for patients with post-COVID-19 fatigue syndrome to enhance both motor function and overall recovery holds paramount significance. Our objective is to assess the effectiveness of rehabilitation in post-COVID-19 patients with upper extremity impairment through the utilization of a hand exoskeleton-based robotic system. Methods: A total of 13 participants experiencing acute or limited functional or strength impairment in an upper extremity due to COVID-19 were enrolled in the study. A structured intervention consisted of 45 min therapy sessions, conducted four times per week over a six-week period, utilizing a hand exoskeleton. The research employed standardized health assessments, motion analysis, and semi-structured interviews for pre-intervention and follow-up evaluations. Paired sample t-tests were employed to statistically analyze the outcomes. Results: The outcomes showed a reduction in overall dependence levels across participants, positive changes in various quality of life-related measurements, and an average increase of 60.4 ± 25.7% and 28.7 ± 11.2% for passive and active flexion, respectively. Conclusions: Our data suggest that hand exoskeleton-based robotic systems hold promise to optimize the rehabilitation outcomes following severe COVID-19. Trial registration: ID NCT06137716 at ClinicalTrials.gov. Full article

(This article belongs to the Special Issue Novel Insights into COVID-19-Associated Complications and Sequelae)

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10 pages, 853 KiB

Open AccessArticle

COVID-19 in a Dutch Nursing Home: A Longitudinal Retrospective Care-Home-Level Case Study on Infection Rate, Survival Rate, and Daily Functioning

by Danielle de Vries, Darwin Röhlinger, Irma Everink, Bjorn Winkens, Joyce Heffels, Adam Gordon and Jos Schols

J. Clin. Med. 2024, 13(1), 149; https://doi.org/10.3390/jcm13010149 - 27 Dec 2023

Cited by 1 | Viewed by 1283

Abstract

During the pandemic, nursing homes in the Netherlands were heavily affected by COVID-19. This study assesses the impact of COVID-19 on infection rate, survival rate, and daily functioning over the course of two years among residents of a nursing home in the Netherlands [...] Read more.

During the pandemic, nursing homes in the Netherlands were heavily affected by COVID-19. This study assesses the impact of COVID-19 on infection rate, survival rate, and daily functioning over the course of two years among residents of a nursing home in the Netherlands that was amongst the first nursing homes to be affected by the pandemic. This retrospective study followed 70 residents during a two-year period, starting in March 2020. Data were collected on baseline characteristics of participants and the onset, duration, and sequelae of COVID-19 infections. Primary outcomes were mortality and infection rate. The secondary outcome was daily functioning using the Barthel Index at intervals of six months. Within two years, 44 (62.9%) residents were diagnosed with COVID-19. During this study, 72.7% (n = 32) of the COVID-positive residents died, of which 22 deaths were related to the COVID-19 infection. Overall mortality was 60% (n = 42), while COVID-related mortality was 31.4% (n = 22). COVID-19 and multimorbidity (>3 morbidities) were independent risk factors for mortality. Barthel Index scores showed no significant difference in daily functioning. Overall, a high COVID-19 infection rate was seen and was the most common cause of death. COVID-19 did not affect functional status over time. Full article

(This article belongs to the Special Issue Novel Insights into COVID-19-Associated Complications and Sequelae)

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12 pages, 1508 KiB

Open AccessArticle

Novel Risks of Unfavorable Corticosteroid Response in Patients with Mild-to-Moderate COVID-19 Identified Using Artificial Intelligence-Assisted Analysis of Chest Radiographs

by Min Hyung Kim, Hyun Joo Shin, Jaewoong Kim, Sunhee Jo, Eun-Kyung Kim, Yoon Soo Park and Taeyoung Kyong

J. Clin. Med. 2023, 12(18), 5852; https://doi.org/10.3390/jcm12185852 - 8 Sep 2023

Viewed by 1402

Abstract

The prediction of corticosteroid responses in coronavirus disease 2019 (COVID-19) patients is crucial in clinical practice, and exploring the role of artificial intelligence (AI)-assisted analysis of chest radiographs (CXR) is warranted. This retrospective case–control study involving mild-to-moderate COVID-19 patients treated with corticosteroids was [...] Read more.

The prediction of corticosteroid responses in coronavirus disease 2019 (COVID-19) patients is crucial in clinical practice, and exploring the role of artificial intelligence (AI)-assisted analysis of chest radiographs (CXR) is warranted. This retrospective case–control study involving mild-to-moderate COVID-19 patients treated with corticosteroids was conducted from 4 September 2021, to 30 August 2022. The primary endpoint of the study was corticosteroid responsiveness, defined as the advancement of two or more of the eight-categories-ordinal scale. Serial abnormality scores for consolidation and pleural effusion on CXR were obtained using a commercial AI-based software based on days from the onset of symptoms. Amongst the 258 participants included in the analysis, 147 (57%) were male. Multivariable logistic regression analysis revealed that high pleural effusion score at 6–9 days from onset of symptoms (adjusted odds ratio of (aOR): 1.022, 95% confidence interval (CI): 1.003–1.042, p = 0.020) and consolidation scores up to 9 days from onset of symptoms (0–2 days: aOR: 1.025, 95% CI: 1.006–1.045, p = 0.010; 3–5 days: aOR: 1.03 95% CI: 1.011–1.051, p = 0.002; 6–9 days: aOR; 1.052, 95% CI: 1.015–1.089, p = 0.005) were associated with an unfavorable corticosteroid response. AI-generated scores could help intervene in the use of corticosteroids in COVID-19 patients who would not benefit from them. Full article

(This article belongs to the Special Issue Novel Insights into COVID-19-Associated Complications and Sequelae)

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12 pages, 2300 KiB

Open AccessArticle

Utility of Serum Ferritin for Predicting Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in Patients with Long COVID

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

J. Clin. Med. 2023, 12(14), 4737; https://doi.org/10.3390/jcm12144737 - 18 Jul 2023

Cited by 9 | Viewed by 5864

Abstract

Objective: The most common symptom of post-acute coronavirus disease 2019 (COVID-19) is fatigue, and it potentially leads to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS); however, a specific prognosticator is lacking. We aimed to elucidate the clinical characteristics of patients who developed ME/CFS after COVID-19. [...] Read more.

Objective: The most common symptom of post-acute coronavirus disease 2019 (COVID-19) is fatigue, and it potentially leads to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS); however, a specific prognosticator is lacking. We aimed to elucidate the clinical characteristics of patients who developed ME/CFS after COVID-19. Methods: In this retrospective observational study, patients who visited Okayama University Hospital for long COVID between February 2021 and March 2022 were investigated. Results: Of the 234 patients, 139 (59.4%) had fatigue symptoms. Fifty patients with fatigue symptoms (21.4%) met the criteria for ME/CFS (ME/CFS group), while the other 89 patients did not (non-ME/CFS group); 95 patients had no fatigue complaints (no-fatigue group). Although the patients’ backgrounds were not significantly different between the three groups, the ME/CFS group presented the highest scores on the self-rating symptom scales, including the Fatigue Assessment Scale (FAS), EuroQol, and the Self-Rating Depression Scale (SDS). Furthermore, serum ferritin levels, which were correlated with FAS and SDS scores, were significantly higher in the ME/CFS group (193.0 μg/L, interquartile range (IQR): 58.8–353.8) than in the non-ME/CFS group (98.2 μg/L, 40.4–251.5) and no-fatigue group (86.7 μg/L, 37.5–209.0), and a high serum ferritin level was prominent in female patients. Endocrine workup further showed that the ME/CFS group had higher thyrotropin levels but lower growth hormone levels in serum and that insulin-like growth factor-I levels were inversely correlated with ferritin levels (R = −0.328, p < 0.05). Conclusions: Serum ferritin level is a possible predictor of the development of ME/CFS related to long COVID, especially in female patients. Full article

(This article belongs to the Special Issue Novel Insights into COVID-19-Associated Complications and Sequelae)

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12 pages, 198 KiB

Open AccessReview

Impact of Pulmonary Comorbidities on COVID-19: Acute and Long-Term Evaluations

by Gabriela Mara, Gheorghe Nini and Coralia Cotoraci

J. Clin. Med. 2025, 14(5), 1446; https://doi.org/10.3390/jcm14051446 - 21 Feb 2025

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Abstract

Background/Objectives: Pulmonary comorbidities, such as chronic obstructive pulmonary disease (COPD), asthma, and interstitial lung diseases (ILDs), have emerged as critical factors influencing the severity and outcomes of COVID-19. This review aims to evaluate the interplay between these comorbidities and COVID-19, both during [...] Read more.

Background/Objectives: Pulmonary comorbidities, such as chronic obstructive pulmonary disease (COPD), asthma, and interstitial lung diseases (ILDs), have emerged as critical factors influencing the severity and outcomes of COVID-19. This review aims to evaluate the interplay between these comorbidities and COVID-19, both during the acute phase and in long-term recovery, focusing on their impact on clinical management and outcomes. Methods: This systematic review examined studies sourced from major medical databases, including PubMed and Scopus, using keywords such as “COVID-19”, “pulmonary comorbidities”, “long COVID”, and “respiratory sequelae”. Peer-reviewed articles published from January 2020 to the present were included, with data extracted to evaluate both the acute and long-term effects of these comorbidities on COVID-19 patients. Results: Patients with COPD demonstrated significantly higher risks of severe COVID-19, including increased hospitalization and mortality. Asthma, while less consistently associated with severe outcomes, showed a variable risk based on disease control. ILDs were strongly correlated with poor outcomes, including higher rates of respiratory failure and mortality. Long-term complications, such as persistent dyspnea, impaired lung function, and structural changes like fibrosis, were prevalent in patients recovering from moderate to severe COVID-19. These complications adversely affected quality of life and increased healthcare dependency. Conclusions: Pulmonary comorbidities amplify both the acute severity and long-term respiratory consequences of COVID-19. Effective management necessitates tailored strategies addressing both phases, integrating rehabilitation and continuous monitoring to mitigate chronic impairments. Future research should prioritize understanding the mechanisms behind these interactions to inform public health interventions and improve patient outcomes. Full article

(This article belongs to the Special Issue Novel Insights into COVID-19-Associated Complications and Sequelae)

20 pages, 904 KiB

Open AccessReview

Long COVID in Children and Adolescents: Mechanisms, Symptoms, and Long-Term Impact on Health—A Comprehensive Review

by Diana-Georgiana Basaca, Iulius Jugănaru, Oana Belei, Delia-Maria Nicoară, Raluca Asproniu, Emil Robert Stoicescu and Otilia Mărginean

J. Clin. Med. 2025, 14(2), 378; https://doi.org/10.3390/jcm14020378 - 9 Jan 2025

Cited by 1 | Viewed by 2623

Abstract

Long COVID, also known as post-acute sequelae of SARS-CoV-2 infection (PASC), is increasingly recognized as a condition affecting not only adults but also children and adolescents. While children often experience milder acute COVID-19 symptoms compared to adults, some develop persistent physical, psychological, and [...] Read more.

Long COVID, also known as post-acute sequelae of SARS-CoV-2 infection (PASC), is increasingly recognized as a condition affecting not only adults but also children and adolescents. While children often experience milder acute COVID-19 symptoms compared to adults, some develop persistent physical, psychological, and neurological symptoms lasting for weeks or months after initial infection. The most commonly reported symptoms include debilitating fatigue, respiratory issues, headaches, muscle pain, gastrointestinal disturbances, and cognitive difficulties, which significantly impact daily activities, schooling, and social interactions. Additionally, many children with long COVID experience psychological symptoms, such as anxiety, depression, mood swings, and irritability, likely exacerbated by prolonged illness and lifestyle disruptions. Risk factors for long COVID in children include pre-existing health conditions such as asthma, obesity, and neurological disorders, with adolescents and females seemingly more affected. Hypothesized mechanisms underlying long COVID include chronic immune dysregulation, persistent viral particles stimulating inflammation, autonomic nervous system dysfunction, and mitochondrial impairment, which may collectively contribute to the variety of observed symptoms. Long-term outcomes remain uncertain; however, long COVID can lead to school absenteeism, social withdrawal, and psychological distress, potentially affecting cognitive development. Severe cases may develop chronic conditions such as postural orthostatic tachycardia syndrome (POTS) and reduced exercise tolerance. This review synthesizes the existing literature on long COVID in children, examining its prevalence, symptomatology, risk factors, and potential mechanisms, with an emphasis on the need for further clinical studies. While existing research largely relies on surveys and self-reported data, clinical assessments are essential to accurately characterize long COVID in pediatric populations and to guide effective management strategies. Full article

(This article belongs to the Special Issue Novel Insights into COVID-19-Associated Complications and Sequelae)

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Open AccessBrief Report

Reduced Salivary Gustin and Statherin in Long-COVID Cohort with Impaired Bitter Taste

by Harika Chowdary, Naomi Riley, Parul Patel, Ana G. Gossweiler, Cordelia A. Running and Mythily Srinivasan

J. Clin. Med. 2024, 13(22), 6816; https://doi.org/10.3390/jcm13226816 - 13 Nov 2024

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Abstract

Background/Objectives: Taste dysfunction is a frequent symptom of acute coronavirus disease (COVID)-19 caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). While the majority of those affected reported recovery over time, emerging data suggest that 20–25% of individuals experience persistent taste dysfunction, [...] Read more.

Background/Objectives: Taste dysfunction is a frequent symptom of acute coronavirus disease (COVID)-19 caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). While the majority of those affected reported recovery over time, emerging data suggest that 20–25% of individuals experience persistent taste dysfunction, constituting a common symptom of long COVID. Gustation is mediated by continuously renewing taste bud cells. A balance between the counteracting processes of cell generation and cell death maintains the homeostatic turnover. Sonic hedgehog (SHH) is a morphogenic protein that promotes taste cell proliferation and differentiation. Enzymatic proteins such as gustin modulate the environment around the taste receptors and influence taste perception. Hence, we hypothesized that increased taste cell turnover and reduced taste-related salivary proteins contribute to the taste dysfunction in long COVID. Methods: Unstimulated whole saliva (UWS) was collected from individuals with long COVID experiencing taste dysfunction after obtaining informed consent. The normal control included archived saliva samples catalogued prior to 2019. Taste perception was objectively determined by the waterless empirical taste test. The SHH, gustin, and inflammatory cytokines in UWS were determined with ELISA. The expressions of epithelial and taste-cell-specific markers in cellular saliva were assessed by immunoflurorescence. Results: Impaired bitter taste was the most common dysfunction in the long-COVID cohort. Salivary gustin was significantly lower in those with long COVID and correlated with lower bitter taste score. Cellular saliva showed keratin-10- and small-proline-rich protein-positive epithelial cells as well as SHH-, occluding- and KCNQ1-positive taste cells. Conclusions: Salivary gustin could be a marker for impaired bitter taste in long COVID. Full article

(This article belongs to the Special Issue Novel Insights into COVID-19-Associated Complications and Sequelae)

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