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Sequelae of COVID-19: Clinical to Prognostic Follow-Up

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

Deadline for manuscript submissions: 30 April 2026 | Viewed by 13896

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Special Issue Editors

Dr. Mariana Tudoran

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Center of Molecular Research in Nephrology and Vascular Disease, Faculty of Medicine, University of Medicine and Pharmacy “Victor Babes” Timisoara, E. Murgu Square, Nr. 2, 300041 Timisoara, Romania
Interests: arterial hypertension; coronary artery disease; heart failure; pulmonary hypertension; cardiovascular alterations in patients with other pathologies
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Dr. Cristina Tudoran

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1. Department VII, Internal Medicine II, Discipline of Cardiology, University of Medicine and Pharmacy “Victor Babes” Timisoara, E. Murgu Square, Nr. 2, 300041 Timisoara, Romania
2. Centre of Molecular Research in Nephrology and Vascular Disease, University of Medicine and Pharmacy “Vic-tor Babes” Timisoara, E. Murgu Square, Nr. 2, 300041 Timisoara, Romania
3. County Emergency Hospital “Pius Brinzeu”, L. Rebreanu, Nr. 156, 300723 Timisoara, Romania
Interests: pulmonary hypertension; heart failure; heart rate variability; myocarditis; pericarditis; COVID-19 and post-acute COVID-19 syndrome
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

A year after the onset of the COVID-19 pandemic, when increasing numbers of patients were observed to have an unusually long and difficult recovery after an acute SARS-CoV-2 infection, researchers suspected that COVID-19 could have long-lasting sequelae. In 2020, post-acute COVID-19 syndrome was first mentioned in the medical literature, defined by the persistence of symptoms between 3 weeks and 3 months after an acute SARS-CoV-2 infection. Unfortunately, this was just the "tip of the iceberg", as several of these patients continued to present complaints or even new symptoms that occurred up to 6 months after contracting the SARS-CoV-2 infection. These subjects were diagnosed as having long COVID, which, according to the World Health Organization, has an incidence of 10–20% of all patients recovering from COVID-19. The symptoms cover a large spectrum since various systems and organs can be affected during the acute infection. The most frequently encountered sequelae are respiratory ones such as interstitial pulmonary fibrosis resulting in respiratory insufficiency, followed by multiple cardiovascular dysfunctions, with the most severe being pulmonary hypertension and chronic heart failure, not to forget neurological and psychiatric alterations, but also the renal, metabolic, hematological, or even gastrointestinal consequences of this disease. It should be mentioned that these sequelae rarely appear isolated; they are frequently associated and interrelated, severely affecting patients′ quality of life.

This Special Issue aims to focus on new insights concerning the underlying pathophysiological mechanisms, diagnosis, management, and complex treatment of COVID-19 sequelae. We welcome the submission of original articles, reviews, and clinical trials focused on new approaches to COVID-19 syndromes.

Dr. Mariana Tudoran
Dr. Cristina Tudoran
Guest Editors

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Keywords

COVID-19
post-COVID-19 syndromes
sequelae of COVID-19
pathophysiological pathways
multiorgan sequelae
long-term management of post-COVID-19 syndromes
quality of life
long-term prognosis of COVID-19

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Published Papers (12 papers)

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18 pages, 641 KB

Open AccessArticle

Pulmonary Embolism in Hospitalized COVID-19 Patients: Incidence, Clinical Predictors, and Short-Term Outcomes

by Cristiana Adina Avram, Maria-Laura Craciun, Ana-Maria Pah, Stela Iurciuc, Simina Crisan, Cristina Vacarescu, Ioana Cotet, Claudia Raluca Balasa Virzob, Dan Alexandru Surducan and Claudiu Avram

J. Clin. Med. 2026, 15(8), 3117; https://doi.org/10.3390/jcm15083117 - 19 Apr 2026

Viewed by 145

Abstract

Background/Objectives: Pulmonary embolism (PE) represents a major thrombotic complication in hospitalized patients with coronavirus disease 2019 (COVID-19), yet data on its incidence, clinical predictors, and short-term outcomes in actual cohorts remain heterogeneous. Methods: We conducted a retrospective observational cohort study including 395 consecutive adults hospitalized with RT-PCR-confirmed COVID-19 at a tertiary infectious diseases center between March 2020 and December 2024. Clinical, laboratory, imaging, and treatment data were extracted from electronic records, and PE was defined by computed tomography pulmonary angiography. Univariable and multivariable logistic regression analyses were used to identify independent predictors of PE in the subset of patients who underwent CTPA (n = 120), in whom PE status was definitively ascertained (47 with PE and 73 without PE). Results: Pulmonary embolism was diagnosed in 47 patients (11.9%). Patients with PE more frequently had prior venous thromboembolism (19.1% vs. 8.3%) and prolonged immobilization (61.7% vs. 23.0%), and were more often admitted to the intensive care unit (12.8% vs. 4.3%) than those without PE. Peak D-dimer levels were almost ten-fold higher in the PE group (median 5322 vs. 529.5 µg/L). In multivariable logistic regression, peak D-dimer was independently associated with PE (per log-unit increase, adjusted OR 3.9, 95% CI 2.1–7.1), and prolonged immobilization conferred a substantially higher risk of PE (adjusted OR 5.1, 95% CI 2.4–10.9). Patients with PE experienced more complex hospital courses and more frequent need for advanced therapies, although in-hospital mortality did not differ significantly between groups. Conclusions: In hospitalized COVID-19 patients, PE is frequent and closely linked to marked D-dimer elevation and acquired in-hospital risk factors, particularly prolonged immobilization. This evidence supports the use of dynamic D-dimer assessment and careful evaluation of immobilization status to improve risk stratification, guide decisions on diagnostic imaging and anticoagulation intensity, and identify patients who may benefit from closer post-discharge cardiovascular follow-up (this hypothesis requires confirmation in future prospective studies). Full article

(This article belongs to the Special Issue Sequelae of COVID-19: Clinical to Prognostic Follow-Up)

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28 pages, 3252 KB

Open AccessArticle

Psychiatric and Neurological Involvement in COVID-19 Hospitalized Patients Through the Global Pandemic in Central Romania

by Claudia Daniela Lupu, Vlad-Dan Cotuțiu and Victoria Birlutiu

J. Clin. Med. 2026, 15(8), 3030; https://doi.org/10.3390/jcm15083030 - 16 Apr 2026

Viewed by 231

Abstract

Background: Neuropsychiatric manifestations are a recognized complication of COVID-19, yet their temporal evolution across pandemic waves remains poorly characterized in hospitalized cohorts. This study examined whether their prevalence and composition changed across five successive waves. Methods: We conducted a retrospective observational study of 1471 hospitalized adults with confirmed Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection at Sibiu County Emergency Clinical Hospital, Romania (March 2020–January 2025), spanning ancestral through Omicron variants. A custom natural language processing pipeline extracted symptoms, medications, and International Classification of Diseases, 10th Revision (ICD-10) codes from electronic medical records. Nine hierarchical clinical clusters were defined; temporal trends were assessed using multivariable logistic regression with age-stratified replication. Results: Severe neurological presentations (stroke, seizures, hemiparesis) increased six-fold from 3.5% in Wave 1 to 20.1% in Wave 5, while psychiatric symptoms (anxiety, insomnia) declined from 13.3% to 4.3%. Overall, neuropsychiatric burden remained stable (~40–45%), revealing a compositional shift. This neurological trend persisted after multivariable adjustment (adjusted odds ratio 4.34, for Wave 5 vs. Wave 1) and within age-stratified subgroups, was inversely associated with respiratory severity and could not be attributed to vaccination status. The composite neurological severity index independently predicted mortality and intensive care unit admission. Conclusions: Neuropsychiatric manifestations in hospitalized Coronavirus disease of 2019 (COVID-19) patients underwent a compositional shift from psychiatric dominance in early waves to severe neurological dominance in later waves, consistent with a transition from reactive psychiatric presentations toward progressive neurological injury. This pattern, largely independent of measured confounders, underscores the need for sustained neurological surveillance beyond the acute respiratory phase. Full article

(This article belongs to the Special Issue Sequelae of COVID-19: Clinical to Prognostic Follow-Up)

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15 pages, 673 KB

Open AccessArticle

Inflammatory Biomarkers and Clinical Outcomes in Hospitalized Patients with COVID-19 and Pre-Existing Heart Failure: A Single-Center Cohort Study

by Maria-Laura Craciun, Adina Cristiana Avram, Ana-Maria Pah, Cristina Vacarescu, Diana-Maria Mateescu, Adrian Cosmin Ilie, Ioana Georgiana Cotet, Claudia Raluca Balasa Virzob, Simina Crisan, Claudiu Avram, Florina Buleu, Daian Ionel Popa, Zorin Petrisor Crainiceanu and Stela Iurciuc

J. Clin. Med. 2026, 15(6), 2209; https://doi.org/10.3390/jcm15062209 - 13 Mar 2026

Cited by 1 | Viewed by 464

Abstract

Background/Objectives: Patients with pre-existing heart failure (HF) represent a clinically vulnerable population with increased susceptibility to adverse outcomes during acute systemic illnesses, including coronavirus disease 2019 (COVID-19). Systemic inflammation is increasingly recognized as a central pathophysiological mechanism linking cardiovascular vulnerability with infection-related organ dysfunction. However, the prognostic role of inflammatory biomarkers in hospitalized COVID-19 patients with pre-existing HF remains incompletely defined. This study aimed to evaluate the association between inflammatory biomarkers and clinical outcomes in this high-risk population. Methods: This retrospective single-center cohort study included 395 consecutive adult patients hospitalized with confirmed COVID-19 between March 2020 and December 2024 at a tertiary referral center. Pre-existing HF was documented in 143 patients (36.2%). Inflammatory biomarkers, including C-reactive protein (CRP), interleukin-6 (IL-6), procalcitonin, and D-dimer, were measured at admission. The primary outcomes were development of sepsis and in-hospital mortality. Multivariable logistic regression models were constructed to identify independent predictors of adverse outcomes after adjustment for demographic characteristics, comorbidities, disease severity, and cardiac biomarkers. Results: Patients with pre-existing HF had significantly higher in-hospital mortality compared with those without HF (11.9% vs. 4.8%, p = 0.016) and showed a trend toward increased intensive care unit admission. HF patients exhibited higher admission IL-6 levels, indicating enhanced inflammatory activation. In univariable analysis, HF was associated with mortality (OR 2.67, 95% CI 1.22–5.83, p = 0.014). After multivariable adjustment, the association between HF and mortality was attenuated, whereas IL-6 remained an independent predictor of mortality (adjusted OR 1.38, 95% CI 1.04–1.82, p = 0.021). Elevated IL-6 and procalcitonin levels were also independently associated with sepsis development. Conclusions: Pre-existing heart failure identifies a population at increased risk of adverse outcomes in hospitalized COVID-19 patients, and this excess risk appears to be partly mediated by systemic inflammatory activation. Interleukin-6 emerged as a key biomarker linking cardiovascular vulnerability, immune dysregulation, and clinical deterioration. These findings support the potential role of inflammation-based risk stratification to improve prognostic assessment and guide personalized management in high-risk patients with underlying cardiovascular disease. Full article

(This article belongs to the Special Issue Sequelae of COVID-19: Clinical to Prognostic Follow-Up)

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14 pages, 907 KB

Open AccessArticle

COVID-19 Fog Symptoms Are Associated with Brain Metabolism and Platelet-to-Lymphocyte Ratio—A Cross-Sectional Analysis of the COVMENT Trial Baseline Data

by Arkadiusz Lubas, Julia Bryłowska, Anna Grzywacz, Bartłomiej Włochacz, Agnieszka Giżewska, Mirosław Dziuk, Anna Klimkiewicz and Jakub Klimkiewicz

J. Clin. Med. 2026, 15(5), 1804; https://doi.org/10.3390/jcm15051804 - 27 Feb 2026

Viewed by 739

Abstract

Background: Post-COVID-19 cognitive impairment, commonly referred to as “brain fog,” represents a significant clinical problem, yet its underlying mechanisms remain incompletely understood. New research indicates that long-term cognitive consequences of SARS-CoV-2 infection may result from chronic immunological dysregulation and neurometabolic changes. Objective: We aimed to assess the associations between cognitive performance, cerebral glucose metabolism, and inflammatory markers in patients with COVID-19 brain fog symptoms. Methods: This study included 47 patients with post-COVID-19 cognitive complaints enrolled in the COVMENT trial. Cognitive performance was assessed using the Montreal Cognitive Assessment (MoCA). Brain glucose metabolism was evaluated with FDG PET-CT, and inflammatory markers, including C-reactive protein (CRP), monocyte-to-lymphocyte ratio, neutrophil-to-lymphocyte ratio, eosinophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio (PLR), were measured. Correlation analyses, logistic regression, and ROC analysis were performed to explore relationships between these factors. Results: A lower score of the MoCA abstraction domain correlated significantly with lower FDG uptake in multiple brain regions, including inferior parietal lobules and precuneus. Among inflammatory markers, only PLR demonstrated significant associations with both brain metabolism and abstraction performance. Lower PLR values were associated with greater neurometabolic impairment, and PLR < 130.1 was associated with abnormal abstraction performance. Conclusions: Post-COVID-19 cognitive dysfunction can be associated with selective neurometabolic alterations in brain regions supporting abstract reasoning. PLR seems to be associated with both cognitive performance and regional brain metabolism, suggesting a potential link between chronic immune dysregulation and neurocognitive impairment in post-COVID-19. Full article

(This article belongs to the Special Issue Sequelae of COVID-19: Clinical to Prognostic Follow-Up)

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15 pages, 835 KB

Open AccessArticle

Acute Pulmonary Edema in COVID-19: Clinical Predictors, Long-Term Pulmonary Sequelae, and Mortality in a Romanian Cohort Study

by Diana-Maria Mateescu, Dragos-Mihai Gavrilescu, Andrei Marginean, Ioana-Georgiana Cotet, Elena-Cristina Guse, Camelia-Oana Muresan, Ana-Olivia Toma, Stela Iurciuc, Adrian-Cosmin Ilie and Alexandra Enache

J. Clin. Med. 2025, 14(22), 8188; https://doi.org/10.3390/jcm14228188 - 18 Nov 2025

Viewed by 1200

Abstract

Background/Objectives: Acute pulmonary edema (APE) has emerged as an overlooked but life-threatening manifestation of COVID-19, reflecting the intersection of inflammatory, endothelial, and cardiac injury pathways. This study aimed to determine the incidence, independent predictors, and long-term pulmonary sequelae of APE in hospitalized COVID-19 patients. Materials and Methods: We conducted a retrospective cohort study including 127 consecutively admitted adults with confirmed SARS-CoV-2 infection at a tertiary-care center in Romania. Demographic, clinical, biochemical, and imaging data were analyzed. Multivariate logistic regression identified independent predictors of APE and in-hospital mortality, while three-month follow-up assessed pulmonary recovery and biomarker dynamics. Results: APE occurred in 36.2% of patients and was associated with a four-fold increase in in-hospital mortality (43.5% vs. 12.3%, p < 0.001). Elevated NT-proBNP, troponin I, and IL-6 levels independently predicted both APE occurrence and mortality. APE patients required more frequent ICU admission (52.2% vs. 18.5%, p < 0.001) and had longer hospital stays. At three months, 39% of APE survivors exhibited fibrotic CT changes, and 37% had restrictive ventilatory defects, correlating with persistently increased NT-proBNP and IL-6 concentrations. Conclusions: Acute pulmonary edema delineates a distinct cardio-inflammatory phenotype of COVID-19, driven by endothelial dysfunction and biomarker-elevated cardiac stress. Early biomarker-guided fluid management and structured multidisciplinary follow-up may mitigate both acute mortality and chronic pulmonary sequelae in post-COVID populations. Full article

(This article belongs to the Special Issue Sequelae of COVID-19: Clinical to Prognostic Follow-Up)

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13 pages, 276 KB

Open AccessArticle

Liver-Related COVID-19 Consequences: Dynamics of Liver Health in 2.5 Years

by Ieva Vanaga, Oksana Kolesova, Aleksandrs Kolesovs, Maija Radzina, Davis Simanis Putrins, Jelena Egle, Sniedze Laivacuma, Jelena Storozenko and Ludmila Viksna

J. Clin. Med. 2025, 14(21), 7604; https://doi.org/10.3390/jcm14217604 - 27 Oct 2025

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Abstract

Objectives: This study aimed to assess the dynamics of liver tests (LT) and detect signs of liver fibrosis and steatosis 2.5 years after the first COVID-19 episode in patients without pre-existing liver-related conditions. Methods: The study included 65 adult patients hospitalized with COVID-19 (including 18 with severe or critical illness) in 2020. After 2.5 years, in addition to regular LT, liver health status was assessed by the FIB-4 index, hyaluronic acid, cytokeratin 18 fragment M30 (serum, ELISA), cardiometabolic risk factors, and the multiparametric ultrasound examination. Results: LT abnormalities in the acute COVID-19 period were observed more frequently (p = 0.036) in patients with severe or critical COVID-19 (83%) than in patients with non-severe COVID-19 (55%). LT dynamics in 2.5 years showed an improvement of liver health status in most patients (p = 0.006). Persistent LT abnormalities were associated with LT abnormalities during hospitalization (p = 0.021). After 2.5 years, the presence of cardiometabolic risk factors and signs of liver fibrosis were associated with the severity of the first COVID-19 episode. However, regression analyses did not support disease severity as a predictor for LT abnormalities and liver stiffness. The latter was predicted by cardiovascular diseases in the anamnesis. Conclusions: In most patients, LT normalized despite potential risk factors. Simultaneously, in some patients, signs of liver fibrosis after COVID-19 might be stimulated by COVID-19-related metabolic dysfunction and the presence of cardiovascular diseases. Full article

(This article belongs to the Special Issue Sequelae of COVID-19: Clinical to Prognostic Follow-Up)

14 pages, 1067 KB

Open AccessArticle

Outcomes, Sequelae, and Ventilatory Strategies in Long COVID Patients with Severe ARDS: A Retrospective Cohort Study

by Diana-Alexandra Mîțu, Florina Buleu, Daian-Ionel Popa, Cosmin Trebuian, Dumitru Sutoi, Adina Coman, Daniel Florin Lighezan, Tiberiu Buleu, Natheer Sliman, Oana Raluca Radbea and Ovidiu Alexandru Mederle

J. Clin. Med. 2025, 14(20), 7223; https://doi.org/10.3390/jcm14207223 - 13 Oct 2025

Viewed by 1056

Abstract

Background and Aims: Severe acute respiratory distress syndrome (ARDS) in patients with long COVID remains associated with extremely high mortality and significant long-term sequelae. Non-invasive ventilatory strategies such as continuous positive airway pressure (CPAP) and high-flow nasal cannula (HFNC) are widely used before endotracheal intubation (ETI). Still, their comparative effectiveness in this population is not well established. Understanding survival outcomes and sequelae can help refine treatment strategies for this high-risk group. This study aimed to evaluate outcomes, sequelae, and treatment strategies in long COVID patients with severe ARDS, focusing on non-invasive ventilatory support before ETI. Materials and Methods: A retrospective cohort analysis was performed using a study comparing severe ARDS patients with and without COVID-19. The inclusion criterion was a Horovitz quotient (PaO₂/FiO₂) < 50 mmHg. Results: The study included a total of 59 patients diagnosed with long COVID-19 ARDS, with a mortality rate of 85%. A significant proportion of the patient population was male, accounting for 75%. The highest survival rate was observed among patients who initially received CPAP support, with a survival rate of 23.08%, in contrast to those treated solely with HFNC or those who alternated between HFNC and CPAP. Among patients who required endotracheal intubation and subsequent mechanical ventilation, survival rates were 40% for those who had previously received CPAP, 10% for those treated with alternating HFNC and CPAP, and 0% for those managed exclusively with HFNC before ETI. Survivors often exhibited sequelae, such as impaired pulmonary function, persistent dyspnea, and diminished physical performance. Conclusions: Patients with long COVID who develop severe ARDS (PaO₂/FiO₂ < 50 mmHg) face exceptionally high ICU mortality, with outcomes determined mainly by age, comorbidities, and profound hypoxemia. Although CPAP showed a trend toward improved survival, the data do not establish superiority and should be regarded as hypothesis-generating. Rather, they highlight the complexity of managing this underrepresented subgroup and underscore the need for larger, multicenter studies with broader inclusion criteria to confirm or refute these preliminary observations. Full article

(This article belongs to the Special Issue Sequelae of COVID-19: Clinical to Prognostic Follow-Up)

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13 pages, 5539 KB

Open AccessArticle

Objective and Subjective Voice Outcomes in Post-COVID-19 Dysphonia: A High-Speed Videoendoscopy Pre–Post Study

by Joanna Jeleniewska, Jakub Malinowski, Ewa Niebudek-Bogusz and Wioletta Pietruszewska

J. Clin. Med. 2025, 14(19), 6861; https://doi.org/10.3390/jcm14196861 - 28 Sep 2025

Viewed by 1199

Abstract

Background/Objectives: The post-COVID-19 condition frequently includes dysphonia. We aimed to assess objective and subjective voice disorders and short-term responses to multimodal therapy in patients with isolated post-COVID-19 dysphonia. Methods: This retrospective, single-center pre–post study screened 244 post-COVID-19 patients; a subset of 14 with isolated dysphonia underwent standardized assessment at baseline and at 1-month follow-up. Patient-reported outcomes (Voice Handicap Index, VHI; Voice-Related Quality of Life, V-RQOL) and endoscopic evaluation were performed using videolaryngostroboscopy (LVS) and high-speed videoendoscopy (HSV) with kymographic analysis to quantify parameters describing vocal fold oscillations. The treatment included short-term systemic corticosteroids, inhaled corticosteroids, hyaluronic-acid inhalations, and structured voice therapy. Results: At baseline, HSV revealed signs of glottal insufficiency—irregular and asymmetric vocal fold motion, reduced amplitude and pliability, a disrupted mucosal wave, and an increased open quotient. At follow-up, HSV showed increased oscillation, amplitude, and cycle regularity with reduced left–right asymmetry and phase differences; phonovibrograms displayed clearer and more structured patterns. Perturbation indices decreased across jitter and shimmer measures, and the mean fundamental frequency was lower. Improvements in instrumental measures aligned with better VHI and V-RQOL scores. Conclusions: In patients with persistent dysphonia after acute SARS-CoV-2 infection, comprehensive ENT evaluation with instrumental laryngeal assessment is warranted. Short-term multimodal management was associated with improvements in both HSV-derived measures and patient-reported outcomes; confirmation in controlled studies is needed. Full article

(This article belongs to the Special Issue Sequelae of COVID-19: Clinical to Prognostic Follow-Up)

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14 pages, 652 KB

Open AccessArticle

Long COVID and Acute Stroke in the Emergency Department: An Analysis of Presentation, Reperfusion Treatment, and Early Outcomes

by Daian-Ionel Popa, Florina Buleu, Aida Iancu, Anca Tudor, Carmen Gabriela Williams, Marius Militaru, Codrina Mihaela Levai, Tiberiu Buleu, Livia Ciolac, Anda Gabriela Militaru and Ovidiu Alexandru Mederle

J. Clin. Med. 2025, 14(18), 6514; https://doi.org/10.3390/jcm14186514 - 16 Sep 2025

Cited by 2 | Viewed by 1630

Abstract

Background and Objectives: Long COVID has been linked with persistent neurological symptoms, but data on its effects on acute stroke presentation, management, and outcomes remain unclear. This study aimed to compare the clinical profile, management, and short-term outcome of acute ischemic stroke patients with and without Long COVID. Materials and Methods: A retrospective cohort study was conducted on 132 patients who presented at admission with code stroke alert in our Emergency Department (ED). Out of those, 26 were identified to have the Long COVID condition and assigned to the Long COVID group, and 106 were without the Long COVID condition and assigned to the No Long COVID group. Baseline demographics, stroke severity by NIHSS (National Institutes of Health Stroke Scale), risk factors, admission symptoms, laboratory findings, Emergency department time targets, reperfusion treatments received, and outcomes between the two groups were compared. Results: There were no significant differences between the two groups in age, gender, baseline NIHSS scores, ED time targets, or laboratory values. The proportion of patients with Long COVID significantly increased among non-smokers (Fisher’s Exact Test chi-squared, p = 0.027). Also, patients suffering from Long COVID exhibited higher incidences of headache (19.2% compared to 5.7%, OR = 3.97, p = 0.040) and facial drooping (42.3% compared to 19.8%, OR = 2.97, p = 0.022). The mechanical thrombectomy was more frequent among the group with Long COVID (30.8% vs. 16.0%), but this difference was not statistically significant. More hemorrhagic transformations happened in the Long COVID group (26.9% vs. 14.2%, p = 0.143). Discharge rates and hospital length of stay in days were similar between groups. Conclusions: Long COVID patients did not present notable differences in emergency department time targets, baseline stroke severity, or short-term outcomes when presenting with code stroke alert. Nevertheless, specific clinical characteristics—such as elevated occurrences of headache and facial drooping—were more frequently observed in patients with Long COVID, alongside non-significant trends indicating a greater utilization of mechanical thrombectomy and increased rates of hemorrhagic transformation. These results imply that Long COVID may have a subtle impact on stroke presentation and potentially on underlying cerebrovascular susceptibility. Further prospective studies with larger sample sizes are necessary to investigate Long COVID’s long-term neurological and vascular consequences. Full article

(This article belongs to the Special Issue Sequelae of COVID-19: Clinical to Prognostic Follow-Up)

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14 pages, 1079 KB

Open AccessArticle

Symptomatic Trends and Time to Recovery for Long COVID Patients Infected During the Omicron Phase

by Hiroshi Akiyama, Yasue Sakurada, Hiroyuki Honda, Yui Matsuda, Yuki Otsuka, Kazuki Tokumasu, Yasuhiro Nakano, Ryosuke Takase, Daisuke Omura, Keigo Ueda and Fumio Otsuka

J. Clin. Med. 2025, 14(14), 4918; https://doi.org/10.3390/jcm14144918 - 11 Jul 2025

Cited by 2 | Viewed by 2726

Abstract

Background: Since the pathophysiology of long COVID is not yet fully understood, there are no specific methods for its treatment; however, its individual symptoms can currently be treated. Long COVID is characterized by symptoms that persist at least 2 to 3 months after contracting COVID-19, although it is difficult to predict how long such symptoms may persist. Methods: In the present study, 774 patients who first visited our outpatient clinic during the Omicron period from February 2022 to October 2024 were divided into two groups: the early recovery (ER) group (370 cases; 47.8%), who recovered in less than 180 days (median 33 days), and the persistent-symptom (PS) group (404 cases; 52.2%), who had symptoms that persisted for more than 180 days (median 437 days). The differences in clinical characteristics between these two groups were evaluated. Results: Although the median age of the two groups did not significantly differ (40 and 42 in ER and PS groups, respectively), the ratio of female patients was significantly higher in the PS group than the ER group (59.4% vs. 47.3%). There were no significant differences between the two groups in terms of the period after infection, habits, BMI, severity of COVID-19, and vaccination history. Notably, at the first visit, female patients in the PS group had a significantly higher rate of complaints of fatigue, insomnia, memory disturbance, and paresthesia, while male patients in the PS group showed significantly higher rates of fatigue and headache complaints. Patients with more than three symptoms at the first visit were predominant in the PS groups in both genders. Notably, one to two symptoms were predominant in the male ER group, while two to three symptoms were mostly reported in the female PS group. Moreover, the patients in the PS group had significantly higher scores for physical and mental fatigue and for depressive symptoms. Conclusions: Collectively, these results suggest that long-lasting long COVID is related to the number of symptoms and presents gender-dependent differences. Full article

(This article belongs to the Special Issue Sequelae of COVID-19: Clinical to Prognostic Follow-Up)

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12 pages, 717 KB

Open AccessSystematic Review

Incident Heart Failure Risk Following COVID-19 Recovery: A Systematic Review and Meta-Analysis

by Ana Maria Mihai, Monica Marc, Florina Lucaciu and Alexandra Sima

J. Clin. Med. 2026, 15(7), 2665; https://doi.org/10.3390/jcm15072665 - 1 Apr 2026

Viewed by 1932

Abstract

Background/Objectives: While acute cardiac injury during COVID-19 is well-documented, the long-term risk of new-onset heart failure (HF) in survivors remains a critical clinical concern. This study aims to quantify the risk of new-onset heart failure during a 25 months prognostic follow-up period following recovery from SARS-CoV-2. Methods: We conducted a systematic review and meta-analysis of nine high-quality studies (n > 400,000 survivors) in accordance with PRISMA 2020 guidelines. Databases including PubMed/MEDLINE and Scopus were searched through January 2026. A quantitative meta-analysis was performed on six studies using a random-effects model to pool adjusted hazard ratios (aHR). Results: The pooled analysis revealed a significant 35% increased risk of new-onset heart failure following COVID-19 recovery (aHR 1.35; 95% CI: 1.14–1.60; p = 0.001). Significant heterogeneity was observed (I² = 92.62%), reflecting diverse risk profiles among survivors. The risk was most pronounced in immunocompromised kidney transplant recipients (aHR 2.32) and younger adults under the age of 65 (aHR 1.53). Subclinical myocardial damage, characterized by reduced left ventricular longitudinal strain, was identified even in survivors who experienced mild initial infections. Conclusions: COVID-19 recovery serves as a significant independent risk factor for chronic heart failure, emphasizing that cardiovascular impact extends far beyond the acute phase. These findings necessitate the implementation of structured cardiovascular monitoring and biomarker screening for at least one year post-infection to address this emerging chronic disease burden. Full article

(This article belongs to the Special Issue Sequelae of COVID-19: Clinical to Prognostic Follow-Up)

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20 pages, 1382 KB

Open AccessSystematic Review

Surgical Timing and Safety of Breast Cancer Operations After COVID-19: A Prospective-Only Meta-Analysis of Cohort Studies

by Ioana-Georgiana Cotet, Diana-Maria Mateescu, Dragos-Mihai Gavrilescu, Andrei Marginean, Stefania Serban, Adrian-Cosmin Ilie, Cristina Guse, Ana-Maria Pah, Marius Badalica-Petrescu, Stela Iurciuc, Maria-Laura Craciun, Adina Avram and Cristina Tudoran

J. Clin. Med. 2026, 15(1), 341; https://doi.org/10.3390/jcm15010341 - 2 Jan 2026

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Abstract

Background: The COVID-19 pandemic raised uncertainties regarding the safe timing of breast cancer surgery after SARS-CoV-2 infection, and robust prospective evidence has remained limited. Methods: We conducted a systematic review and meta-analysis of prospective cohort studies (2020–2024) investigating postoperative outcomes in breast cancer patients with confirmed SARS-CoV-2 infection ≤90 days before surgery versus contemporaneous non-infected controls treated at the same institutions and in the same period. PROSPERO CRD420251174613. Random-effects models (DerSimonian–Laird with Hartung–Knapp adjustment) were used to pool odds ratios (ORs) and 95% confidence intervals (CIs). Study quality was assessed with the Newcastle–Ottawa Scale, and certainty of evidence was rated using GRADE. Results: Twelve prospective cohort studies, including 7812 patients, compared breast cancer surgery after recent confirmed SARS-CoV-2 infection over 90 days with contemporaneous non-infected controls treated at the same centres. Overall, recent infection was associated with higher 30-day postoperative complications (Clavien–Dindo ≥ II) compared to. non-infected patients (OR 2.01, 95% CI 1.44–2.81) and increased venous thromboembolism (3.6%vs. 1.2%; OR 3.12, 95% CI 1.29–7.55). Early surgery 14 days after infection carried the highest risk of complications (OR 4.38, 95 CI 2.31–8.30), whereas operations performed ≥6 weeks yielded outcomes comparable to non-infected controls (OR 1.03, 95 CI 0.81–1.31); 30-day mortality remained very low (0.3). Conclusions: Breast cancer surgery after SARS-CoV-2 infection is associated with excess perioperative risk only when performed within the first two weeks. Delaying surgery to approximately six weeks minimises complications and VTE without compromising short-term safety. Full article

(This article belongs to the Special Issue Sequelae of COVID-19: Clinical to Prognostic Follow-Up)

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