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Article

Exploratory, Cross-Sectional Observations on Post-COVID-19 Respiratory Symptoms: A Multivariable Analysis

by
Patchareeya Amput
1,2,*,
Arunrat Srithawong
1,
Ajchamon Thammachai
1 and
Sirima Wongphon
3
1
Department of Physical Therapy, School of Allied Health Sciences, University of Phayao, Phayao 56000, Thailand
2
Unit of Excellence of Human Performance and Rehabilitations, University of Phayao, Phayao 56000, Thailand
3
Department of Traditional Chinese Medicine, School of Public Health, University of Phayao, Phayao 56000, Thailand
*
Author to whom correspondence should be addressed.
COVID 2025, 5(11), 191; https://doi.org/10.3390/covid5110191 (registering DOI)
Submission received: 21 October 2025 / Revised: 3 November 2025 / Accepted: 6 November 2025 / Published: 8 November 2025
(This article belongs to the Section COVID Clinical Manifestations and Management)
Versions Notes

Abstract

Background: This cross-sectional study reports exploratory observations on respiratory symptom patterns in individuals with prior coronavirus disease 2019 (COVID-19), evaluating associations with exercise habits, number of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection episodes, vaccine doses received, body mass index (BMI), age, sex, and comorbidities. Methods: A total of 240 participants were assessed for age, sex, height, weight, BMI, comorbidities, SARS-CoV-2 infection episodes, vaccine doses received, and exercise habits; the self-reported duration of symptomatic periods was summarized descriptively and was not modeled as an exposure or outcome. Results: Compared with the first SARS-CoV-2 infection episode (reference), patients who experienced a second episode had higher odds of dyspnea (adjusted odds ratio; OR = 7.61; 95% confidence interval CI = 1.54–37.66). In univariate analysis, patients who received three vaccine doses had lower odds of dyspnea than those who received two doses (OR = 0.39; 95% CI = 0.16–0.98), but this association was not significant after adjustment (adjusted OR = 0.46; 95% CI = 0.13–1.63). After adjustment, patients who exercised had lower odds of secretion compared with those who did not (adjusted OR = 0.30; 95% CI = 0.12–0.73). Conclusions: These cross-sectional, hypothesis-generating observations suggest higher adjusted odds of dyspnea among individuals with repeat infection and lower adjusted odds of sputum among those reporting regular exercise; estimates are imprecise and subject to residual confounding due to unbalanced group sizes. Confirmation in larger, longitudinal cohorts is required.

1. Introduction

The coronavirus disease 2019 (COVID-19) pandemic has led to considerable global illness and death. Both the immediate and prolonged effects of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection present challenges in supporting the recovery of COVID-19 survivors [1]. Post-COVID-19 syndrome encompasses a range of symptoms, including cardiovascular, pulmonary, and neuromuscular issues, as well as other physical and psychological impacts [1]. Some post-COVID-19 patients exhibit symptoms like cough, fever, dyspnea, and fatigue, while others may experience no symptoms at all [2]. Several studies have identified various factors influencing the development and persistence of COVID-19 symptoms, including chronic conditions, underlying diseases, and age [3,4].
Underlying diseases pose significant risk factors for COVID-19 patients. The most common underlying conditions are hypertension, cardiovascular diseases, and diabetes, respectively [5]. In addition, chronic kidney disease, chronic obstructive pulmonary disease (COPD), smoking, and malignancy are also among the most prevalent conditions in COVID-19 patients [6]. Furthermore, previous studies have reported that COVID-19 patients with chronic comorbidities, obesity, and advanced age face a high risk of severe outcomes and mortality [7,8,9]. Consequently, adults and older adults with weakened immune systems are more susceptible to SARS-CoV-2 infection. However, improving immune function through increased physical activity could help mitigate this risk.
Several studies have shown that physical activity strengthens the immune system and enhances the body’s ability to defend against infections [10,11]. Additionally, moderate-intensity aerobic exercise has been found to protect against respiratory infection [12,13,14]. Individuals who engage in moderate exercise experience a lower incidence of infection compared to those who are completely sedentary [15]. Furthermore, engaging in moderate-intensity aerobic exercise for 20–40 min daily can positively influence the immune system [16]. Exercises can stimulate the release of muscle-derived cytokines (myokines), which help maintain immunity and enhance the body’s resistance to infection [11]. Additionally, physical inactivity among individuals with COVID-19 disease had higher rates of intensive care unit (ICU) admission and hospitalization compared to those who were physically active [17]. However, evidence remains limited regarding factors influencing respiratory symptom patterns in COVID-19. Therefore, this study aimed to describe exploratory, cross-sectional associations between exercise habits, the number of SARS-CoV-2 infection episodes, the number of vaccine doses received, BMI, age, sex, comorbidities and respiratory symptoms; the duration of symptomatic periods was collected for descriptive context but was not modeled.

2. Materials and Methods

2.1. Study Design

A cross-sectional correlational design was used to assess exploratory associations among exercise habits, the number of SARS-CoV-2 infection episodes, the number of vaccine doses received, BMI, age, sex, and comorbidities and respiratory symptom outcomes; the duration of symptomatic periods was summarized descriptively and was not modeled.

2.2. Participants

A total of 240 participants were included. The sample size was calculated using power = 0.80, with an alpha of 0.05, and effect size r = 0.16 [18]. The participants recruited were 18 years or older, had a history of COVID-19 disease, and had a confirmed SARS-CoV-2 infection through a polymerase chain reaction (PCR) or antigen test kit (ATK) before the study procedures. Individuals who did not provide informed consent were excluded. This study was approved by the Clinical Research Ethics Committee of the University of Phayao, Phayao, Thailand (HREC-UP-HSST 1.2/170/67, 31 October 2024).

2.3. Procedure

Participants were evaluated for baseline demographic variables, including age, sex, height, weight, body mass index (BMI), as well as clinical information such as comorbidities, the number of SARS-CoV-2 infection episodes, the number of vaccine doses received, exercise habits, and the self-reported duration of symptomatic periods associated with COVID-19 disease, which we summarized descriptively and did not include in multivariable models.

2.4. Statistical Analysis

Demographic characteristics were summarized using frequency, mean, median, standard deviation, range, and percentile (P25th–P75th) as appropriate. Normality was examined using the Kolmogorov–Smirnov and Shapiro–Wilk tests. Models 1 and 2 adjusted for the same covariates (age, HT, DM, BMI, and exercise habit); the difference between models lies in the exposure of interest: Model 1 examined reinfection (second vs. first SARS-CoV-2 episode), whereas Model 2 examined vaccine doses (three vs. two).
Exposure coding and reference groups:
- Model 1 (infection episodes): exposure of interest = second SARS-CoV-2 infection episode (coded 1); reference = first episode (coded 0).
- Model 2 (vaccine doses): exposure of interest = three vaccine doses (coded 1); reference = two doses (coded 0).
- Model 3 (exercise status): exposure of interest = any regular exercise (≥1 time/week; coded 1); reference = no exercise (coded 0).
Covariate adjustments:
- Model 1 adjusted for age, hypertension (HT), diabetes mellitus (DM), BMI, and exercise habit (plus exposure).
- Model 2 adjusted for age, HT, DM, BMI, and exercise habit (plus exposure).
- Model 3 adjusted for age, HT, DM, BMI (plus exposure).
Age and BMI were modeled as continuous variables. A two-sided p-value < 0.05 was considered statistically significant. Given the pronounced imbalance between exposure and reference groups in all three models, we report n (%) by group in the Results/tables, interpret adjusted estimates cautiously, and frame findings as exploratory, pending confirmation in larger, better-balanced cohorts.

3. Results

3.1. Participants Characteristics

A total of 240 participants were included, with an equal distribution of males (50.0%) and females (50.0%). Most participants (88.3%) had no underlying disease. The majority (90.0%) experienced only one SARS-CoV-2 infection, and 82.5% received two vaccine doses. Regarding exercise habits, 17.5% did not exercise, while the remainder exercised 1–4 times per week. The average age was 47.79 ± 12.67 years, weight 57.07 ± 9.72 kg, height 1.63 ± 0.07 m, and BMI 21.38 ± 2.38 kg/m2. The average symptomatic period for COVID-19 was 5.10 ± 0.30 days (Table 1).

3.2. Respiratory Symptoms by Infection Episode (Table 2)

Among participants, 216 had the first SARS-CoV-2 infection and 24 had a second infection. Adjusted logistic regression showed that participants with a second infection had higher odds of dyspnea compared with the first infection (adjusted OR = 7.61; 95% CI = 1.54–37.66), indicating that reinfection may increase the risk of respiratory difficulty. No significant differences were observed for cough, fatigue, or secretion after adjustment.
Table 2. Prevalence of health symptoms related to the first vs. second SARS-CoV-2 infection episodes (n = 240).
Table 2. Prevalence of health symptoms related to the first vs. second SARS-CoV-2 infection episodes (n = 240).
SymptomsTotal
(n = 240)		First Episode (n = 216)Second Episode (n = 24)Univariate AnalysisMultivariate Analysis
Crude OR95% CIAdjusted OR95% CI
Dyspnea65 (27.1)58 (26.9)7 (29.2)1.120.44, 2.847.611.54, 37.66 *
Fever240 (100.0)216 (100.0)24 (100.0)----
Cough111 (46.3)100 (46.3)11 (45.8)0.980.42, 2.291.590.62, 4.05
Fatigue19 (7.9)17 (7.9)2 (8.3)1.060.23, 4.914.680.46, 47.51
Secretion117 (48.8)105 (48.6)12 (50.0)1.060.46, 2.461.600.65, 3.99
Notes: Logistic regressions adjusted for age, HT, DM, BMI, and exercise habit; exposure = second SARS-CoV-2 infection episode (interest), reference = first episode. Group sizes: first episode n = 216 (90.0%), second episode n = 24 (10.0%). OR = odds ratio; CI = confidence interval; * p < 0.05. “-” indicates that the value could not be calculated due to no variation between groups.

3.3. Respiratory Symptoms by Vaccine Doses (Table 3)

Participants receiving three vaccine doses (n = 42) showed lower unadjusted odds of dyspnea compared with those receiving two doses (OR = 0.39; 95% CI = 0.16–0.98). However, after adjusting for age, HT, DM, BMI, and exercise habit, this association was not statistically significant (adjusted OR = 0.46; 95% CI = 0.13–1.63), suggesting potential confounding. No significant associations were observed for cough, fatigue, or secretion.
Table 3. Prevalence of health symptoms related to COVID-19 infection between patients who received the vaccine two and three times (n = 240).
Table 3. Prevalence of health symptoms related to COVID-19 infection between patients who received the vaccine two and three times (n = 240).
SymptomsTotal
(n = 240)		Two Doses
(n = 198)		Three Doses
(n = 42)		Univariate AnalysisMultivariate Analysis
Crude OR95% CIAdjusted OR95% CI
Dyspnea65 (27.1)59 (29.6)6 (14.3)0.390.16, 0.98 *0.460.13, 1.63
Fever240 (100.0)198 (100.0)42 (100.0)----
Cough111 (46.3)95 (48.0)16 (38.1)0.670.54, 1.320.900.42, 1.91
Fatigue19 (7.9)17 (8.6)2 (4.8)0.530.12, 2.401.450.25, 8.57
Secretion117 (48.8)101 (51.0)16 (38.1)0.590.30, 1.670.740.35, 1.55
Notes: Logistic regressions adjusted for age, HT, DM, BMI, and exercise habit; exposure = three vaccine doses (interest), reference = two doses. Group sizes: two doses n = 198 (82.5%), three doses n = 42 (17.5%). OR = odds ratio; CI = confidence interval; * p < 0.05. “-” indicates that the value could not be calculated due to no variation between groups.

3.4. Respiratory Symptoms by Exercise Habit (Table 4)

Participants who exercised regularly (≥1 time/week; n = 198) had lower adjusted odds of secretion compared with those who did not exercise (adjusted OR = 0.30; 95% CI = 0.12–0.73), suggesting that regular exercise may be associated with improved airway clearance. No significant differences were observed for dyspnea, cough, or fatigue, although crude proportions were similar.
Table 4. Prevalence of health symptoms among patients who exercised and those who did not exercise (n = 240).
Table 4. Prevalence of health symptoms among patients who exercised and those who did not exercise (n = 240).
SymptomsTotal
(n = 240)		Exercise
(n = 198)		No Exercise (n = 42)Univariate AnalysisMultivariate Analysis
Crude OR95% CIAdjusted OR95% CI
Dyspnea65 (27.1)61 (30.8)4 (9.5)4.231.45, 12.320.330.64, 1.65
Fever240 (100.0)198 (100.)42 (100.0)----
Cough111 (46.3)95 (48.0)16 (38.1)1.500.76, 2.970.480.20, 1.15
Fatigue19 (7.9)19 (19.6)0 (0)----
Secretion117 (48.8)96 (48.5)21 (50.0)0.940.48, 1.830.300.12, 0.73 *
Notes: Logistic regressions adjusted for age, HT, DM, BMI; exposure = any regular exercise (≥1 time/week; interest), reference = no exercise. Group sizes: any exercise n = 198 (82.5%), no exercise n = 42 (17.5%). OR = odds ratio; CI = confidence interval; * p < 0.05. Crude secretion proportions were similar between groups (48.5% vs. 50.0%); adjusted estimates may reflect covariate imbalances and should be interpreted cautiously in light of low EPV. “-” indicates that the value could not be calculated due to no variation between groups.

4. Discussion

This study examined exploratory, cross-sectional associations between exercise habits, the number of SARS-CoV-2 infection episodes, the number of vaccine doses received, BMI, age, sex, comorbidities and respiratory symptom outcomes among individuals with prior COVID-19; symptomatic duration was collected for descriptive context and was not modeled. In adjusted analyses, participants with a second SARS-CoV-2 infection episode had higher odds of dyspnea than those with a first-time episode (adjusted OR 7.61; 95% CI 1.54–37.66). Although the direction of this association aligns with prior reports that repeated infections and prolonged illness courses may exacerbate respiratory symptoms [19,20,21], the wide confidence interval indicates imprecision and potential instability related to small event counts and unbalanced groups. Prior studies have also identified predictors of persistent dyspnea after COVID-19 [22]. Reinfection could compound these risks through mechanisms such as ongoing airway inflammation, immune dysregulation, or fibrotic remodeling [23]; however, these mechanistic explanations are speculative in this cross-sectional context. Preventive strategies (e.g., up-to-date vaccination, infection control measures) and clinical follow-up for individuals with recurrent infections remain prudent, while prospective studies are needed to determine whether early interventions (including pulmonary rehabilitation) mitigate longer-term respiratory sequelae.
In univariate analyses, participants who received three vaccine doses had lower odds of dyspnea versus those with two doses (OR 0.39; 95% CI 0.16–0.98); however, this association was attenuated and not statistically significant after adjustment (adjusted OR 0.46; 95% CI 0.13–1.63), consistent with confounding. Confounding by indication is plausible, whereby individuals at higher baseline risk (e.g., due to comorbidities) preferentially receive additional booster doses [24]. While vaccines reduce the severity of COVID-19 disease, local and systemic reactions are generally less frequent after a homologous mRNA booster, that is, a third dose of the same mRNA vaccine used in the primary two-dose series, than after the second dose of the primary series [25]. Other factors, such as underlying lung disease or prior SARS-CoV-2 infection, may therefore better explain reports of dyspnea than vaccine dose number alone [26]. Longitudinal studies with detailed clinical histories are needed to clarify these relationships.
We observed that individuals who exercised had lower odds of secretion after adjustment (adjusted OR = 0.30; 95% CI = 0.12–0.73). Exercise may improve pulmonary function and promote mucociliary clearance, thereby aiding the removal of mucus and pathogens from the respiratory tract [27,28]. Techniques such as postural drainage and active cycle of breathing improve airway clearance and lung function [29,30], and exercise-induced increases in ventilation and respiratory muscle engagement may further support mucus mobilization [31,32]. Notably, crude secretion proportions were very similar between the exercise and no-exercise groups (48.5% vs. 50.0%), yet the adjusted OR was statistically significant. This discrepancy can arise when covariates (e.g., age, comorbidities) are imbalanced across exposure groups, yielding different conditional (adjusted) versus marginal (crude) estimates. Given the small absolute difference, limited EPV, and group-size imbalance, the clinical significance is uncertain; we therefore present this finding as hypothesis-generating pending replication.

Limitations of This Study

A key limitation is the pronounced imbalance between exposure and reference groups across models. Despite an adequate overall sample size (n = 240), the exposure groups (e.g., second episode; three vaccine doses; no exercise) were relatively small in some analyses, leading to low EPV and sparse-data issues. These conditions can yield unstable or exaggerated adjusted estimates, wide confidence intervals, and potential (quasi-) separation, complicating inference. Accordingly, adjusted results should be interpreted with caution and viewed as exploratory, pending confirmation in larger, better-balanced cohorts. In addition, cardiovascular diseases were reported by very few participants and therefore were not included as a covariate in the multivariable models, which may limit the generalizability of the findings. Furthermore, the cross-sectional design, potential recall bias (self-reported symptoms/duration), and unmeasured or residual confounding highlight the need for future longitudinal research with objective pulmonary function testing and controlled exercise interventions.

5. Conclusions

In this cross-sectional sample, we observed higher adjusted odds of dyspnea among participants with repeat infection (adjusted OR 7.61; 95% CI 1.54–37.66) and lower adjusted odds of sputum among those reporting regular exercise (adjusted OR 0.30; 95% CI 0.12–0.73). These observational signals are exploratory, imprecise due to small event counts and unbalanced groups, and may reflect residual confounding. They should be interpreted as hypotheses to be tested in larger, longitudinal studies.

Author Contributions

Conceptualization, P.A. and A.S.; Methodology, P.A. and A.S.; Formal Analysis, P.A. and A.T.; Investigation, P.A., A.S. and S.W.; Data Curation, P.A., A.S., A.T. and S.W.; Writing, P.A. and A.S.; Original Draft Preparation, P.A. and A.S.; Writing—Review and Editing, P.A. All authors have read and agreed to the published version of the manuscript.

Funding

This research was supported by University of Phayao and Thailand Science Research and Innovation Fund (Fundamental Fund 2026, Grant No. 2264).

Institutional Review Board Statement

The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Institutional Review Board of The Human Ethical Committee at the University of Phayao, Phayao, Thailand (HREC-UP-HSST 1.2/170/67, 31 October 2024).

Informed Consent Statement

Informed consent was obtained from all subjects involved in the study.

Data Availability Statement

The original contributions presented in this study are included in the article. Further inquiries can be directed to the corresponding author(s).

Acknowledgments

We would like to thank all the volunteers who participated in this study.

Conflicts of Interest

The authors declare no conflicts of interest.

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Table 1. Demographic data of participants (N = 240).
Table 1. Demographic data of participants (N = 240).
Parametersn (%)Mean ± SD
(Min–Max)
Gender   Male
   Female		120 (50.00)
120 (50.00)
Health Status
   Underlying disease with HT13 (5.40)
   Underlying disease with DM8 (3.30)
   Both underlying disease7 (2.90)
   No underlying disease212 (88.30)
Number of SARS-CoV-2 Infection Episodes
   1 time216 (90.00)
   2 times24 (10.00)
Number of Vaccine Doses Received
   2 times198 (82.50)
   3 times42 (17.50)
Exercise Habit
   1 time/week35 (14.60)
   2 times/week81 (33.80)
   3 times/week81 (33.90)
   4 times/week1 (0.40)
   No exercise habit 42 (17.50)
Age 47.79 ± 12.67 (20.00–69.00)
Weight (kg) 57.07 ± 9.72 (6.00–18.00)
Height (m) 1.63 ± 0.07 (1.50–1.78)
Body Mass Index (kg/m2) 21.38 ± 2.38 (16.73–25.95)
Duration of Symptomatic Periods in COVID-19 Disease (Day) 5.10 ± 0.30 (5.00–6.00)
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MDPI and ACS Style

Amput, P.; Srithawong, A.; Thammachai, A.; Wongphon, S. Exploratory, Cross-Sectional Observations on Post-COVID-19 Respiratory Symptoms: A Multivariable Analysis. COVID 2025, 5, 191. https://doi.org/10.3390/covid5110191

AMA Style

Amput P, Srithawong A, Thammachai A, Wongphon S. Exploratory, Cross-Sectional Observations on Post-COVID-19 Respiratory Symptoms: A Multivariable Analysis. COVID. 2025; 5(11):191. https://doi.org/10.3390/covid5110191

Chicago/Turabian Style

Amput, Patchareeya, Arunrat Srithawong, Ajchamon Thammachai, and Sirima Wongphon. 2025. "Exploratory, Cross-Sectional Observations on Post-COVID-19 Respiratory Symptoms: A Multivariable Analysis" COVID 5, no. 11: 191. https://doi.org/10.3390/covid5110191

APA Style

Amput, P., Srithawong, A., Thammachai, A., & Wongphon, S. (2025). Exploratory, Cross-Sectional Observations on Post-COVID-19 Respiratory Symptoms: A Multivariable Analysis. COVID, 5(11), 191. https://doi.org/10.3390/covid5110191

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