European Journal of Cardiovascular Medicine

The COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has had widespread global health implications. While the majority of patients recover within weeks of infection, a considerable subset continues to experience persistent symptoms that last for months, a condition now recognized as Long COVID or Post-Acute Sequelae of SARS-CoV-2 infection (PASC) (1). These lingering effects often extend beyond the respiratory system, involving neurological, cardiovascular, gastrointestinal, and psychological domains, making Long COVID a complex, multisystem disorder requiring comprehensive evaluation (2,3).

Pulmonary complications, including impaired diffusion capacity, dyspnea, and reduced exercise tolerance, are among the most frequently reported symptoms post-COVID-19 (4). Studies have demonstrated long-term impairment in lung function, particularly a reduction in diffusing capacity for carbon monoxide (DLCO), even in patients who had mild to moderate acute illness (5). Concurrently, neurological manifestations such as brain fog, memory loss, and peripheral neuropathy are also common, with evidence suggesting direct viral invasion, neuroinflammation, and microvascular injury as potential etiologies (6,7).

Moreover, the psychological impact of COVID-19 is profound. Many patients report anxiety, depression, and post-traumatic stress symptoms months after infection, which significantly deteriorates their overall quality of life (8). The bidirectional interaction between psychological stress and immune dysregulation may exacerbate or prolong physical symptoms, further complicating the recovery process (9).

Given the multifaceted nature of Long COVID, a siloed approach to care often proves inadequate. Emerging evidence supports the integration of multidisciplinary strategies, combining expertise in pulmonology, neurology, and mental health, to address the varied and overlapping symptomatology of affected individuals (10). However, there is limited empirical data evaluating the effectiveness of such integrated care models.

This study aims to assess the clinical outcomes of a multidisciplinary intervention program targeting pulmonary, neurological, and psychological components in patients suffering from Long COVID, thereby highlighting the potential benefits of a collaborative treatment framework.

A total of 120 adult patients (aged 20–65 years) with a prior confirmed diagnosis of SARS-CoV-2 infection (by RT-PCR or antigen test) and persistent symptoms extending beyond 12 weeks from the acute phase were included. Exclusion criteria were pre-existing chronic respiratory or neurological disorders, psychiatric illness prior to COVID-19, or incomplete medical records.

Clinical Assessment Protocol
Each participant underwent a structured, multidisciplinary evaluation involving pulmonology, neurology, and psychology departments. The assessment was conducted at baseline and repeated after a 12-week intervention period.

• Pulmonary Evaluation:
  Pulmonary function tests (PFTs), including forced vital capacity (FVC), forced expiratory volume in 1 second (FEV₁), and diffusion capacity of the lungs for carbon monoxide (DLCO), were measured using a standardized spirometer in accordance with American Thoracic Society guidelines. Patients also completed the Modified Medical Research Council (mMRC) Dyspnea Scale.
• Neurological Evaluation:
  Neurological function was assessed using the Montreal Cognitive Assessment (MoCA) to screen for cognitive deficits. Peripheral neuropathy was screened through nerve conduction studies where clinically indicated. Fatigue levels were measured using the Fatigue Severity Scale (FSS).
• Psychological Evaluation:
  Mental health was assessed using validated scales: the Generalized Anxiety Disorder 7-item (GAD-7) scale for anxiety, and the Patient Health Questionnaire-9 (PHQ-9) for depressive symptoms. Quality of life was evaluated using the EQ-5D-5L questionnaire.

Intervention Strategy
Participants were enrolled in a 12-week personalized care program. Pulmonary rehabilitation included supervised breathing exercises, aerobic training, and inspiratory muscle training. Neurological rehabilitation consisted of cognitive therapy sessions and memory exercises. Psychological support involved weekly counseling, mindfulness-based cognitive therapy, and pharmacological management when necessary.

Statistical Analysis
Data were analyzed using SPSS version 25.0 (IBM Corp., Armonk, NY). Descriptive statistics were used to summarize demographic and clinical data. Paired t-tests were employed to compare baseline and post-intervention scores for continuous variables. A p-value of less than 0.05 was considered statistically significant.

Out of the 120 participants enrolled, 114 completed the 12-week multidisciplinary intervention program (dropout rate: 5%). The mean age of the study population was 43.2 ± 11.8 years, with 52.6% males and 47.4% females. Baseline characteristics, including symptom duration and comorbidities, are summarized in Table 1.

Pulmonary Outcomes
At baseline, 82 patients (71.9%) exhibited reduced DLCO values (<80% predicted), with a mean DLCO of 65.3 ± 8.7%. Following 12 weeks of pulmonary rehabilitation, there was a significant improvement in DLCO, with post-intervention mean values rising to 76.4 ± 7.2% (p < 0.001). Similarly, improvements were noted in FEV₁ and FVC values. Detailed pulmonary function test comparisons are provided in Table 2.

Neurological Outcomes
Cognitive dysfunction, as indicated by MoCA scores <26, was observed in 67 participants (58.7%) at baseline. After 12 weeks of neurocognitive therapy, the mean MoCA score increased from 23.1 ± 2.4 to 26.2 ± 2.1 (p = 0.002). Fatigue Severity Scale scores also improved, declining from a baseline mean of 5.6 ± 1.0 to 3.8 ± 1.1 post-intervention (p < 0.01) (Table 3).

Psychological Outcomes
A majority of the patients (n=75, 65.8%) demonstrated moderate to severe anxiety (GAD-7 ≥10) and depression (PHQ-9 ≥10) at baseline. After 12 weeks of structured psychological support, significant reductions were observed in both anxiety and depression scores. The mean GAD-7 score decreased from 11.2 ± 2.9 to 6.1 ± 2.5, while the PHQ-9 score dropped from 12.8 ± 3.2 to 7.3 ± 2.8 (p < 0.001 for both comparisons). These findings are presented in Table 4.

Quality of Life
Improvement in overall quality of life was noted in 82% of patients based on EQ-5D-5L index values, which improved from 0.64 ± 0.15 to 0.81 ± 0.12 post-intervention (p < 0.001), as shown in Table 5.

Table 1: Baseline Demographic and Clinical Characteristics (n=114)

Table 2: Pulmonary Function Test Results (Baseline vs Post-Intervention)

Table 3: Neurological Parameters (Baseline vs Post-Intervention)

Table 4: Psychological Assessment Scores (Baseline vs Post-Intervention)

Table 5: Quality of Life (EQ-5D-5L Index)

The present study provides compelling evidence supporting the effectiveness of a multidisciplinary approach in managing Long COVID symptoms, particularly those involving pulmonary, neurological, and psychological domains. Post-COVID syndrome is now well-recognized as a complex condition with varied presentations, affecting nearly one-third of recovered patients and often leading to long-term disability if not appropriately addressed (1,2).

In our cohort, a significant proportion of patients exhibited impaired pulmonary function, particularly reduced DLCO values at baseline. This finding is consistent with earlier reports that describe persistent pulmonary sequelae, even in individuals who experienced mild to moderate acute COVID-19 illness (3,4). After a 12-week structured pulmonary rehabilitation program, a marked improvement was observed in key parameters such as FEV₁, FVC, and DLCO. These outcomes align with previous studies that emphasize the role of rehabilitation exercises in restoring lung capacity and reducing dyspnea in Long COVID patients (5,6).

Neurological manifestations, notably cognitive deficits and fatigue, were prevalent in our study. These are among the most reported symptoms in post-COVID patients and are believed to result from a combination of factors, including neuroinflammation, microvascular injury, and autoimmune responses triggered by the viral infection (7,8). The improvement in MoCA scores and reduction in fatigue severity after neurocognitive rehabilitation demonstrate the reversibility of some neurological impairments and highlight the importance of early intervention. Similar benefits have been documented in other rehabilitation trials focusing on cognitive dysfunction in post-viral syndromes (9,10).

Psychological burden, including anxiety and depression, also featured prominently in our study population. More than 65% of patients demonstrated clinically significant symptoms at baseline, which is comparable to rates reported in global meta-analyses on post-COVID mental health (11). Psychological interventions, such as cognitive behavioral therapy and mindfulness-based stress reduction, were associated with substantial improvements in both GAD-7 and PHQ-9 scores in our study. These findings corroborate previous literature emphasizing the need for integrating mental health services into Long COVID care models (12,13).

Importantly, the integration of multidisciplinary care not only improved symptom-specific outcomes but also significantly enhanced overall quality of life, as measured by the EQ-5D-5L index. This supports the broader view that managing Long COVID requires not just symptom resolution but also restoration of functional well-being and social participation (14,15). The model of care used in this study demonstrates a scalable, patient-centered strategy that can be adapted in other clinical settings to improve outcomes for Long COVID patients.

However, this study has certain limitations. The sample size was modest, and the follow-up period was relatively short. Further, the absence of a control group limits the ability to attribute improvements solely to the interventions provided. Long-term studies with randomized control designs are warranted to evaluate the sustainability of these improvements and to identify which patient subgroups benefit most from specific interventions.

In conclusion, the findings reinforce the importance of a multidisciplinary approach in managing Long COVID. The coordinated involvement of pulmonologists, neurologists, and mental health professionals offers a comprehensive strategy to address the heterogeneous and persistent nature of this condition. Future healthcare models must evolve to accommodate the complex recovery pathways of COVID-19 survivors.

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