Background
Dyspnea is a common symptom following COVID-19 and has a significant impact on quality of life [
1‐
3]; however, our understanding of the mechanisms of dyspnea in this specific context also remain limited. Although some patients have cardiopulmonary abnormalities post-COVID, dyspnea can persist in others despite improvements in and normalization of cardiopulmonary function [
4‐
7].
The underlying pathophysiology behind this ‘unexplained’ dyspnea remains unknown, with previous studies showing conflicting results. While some studies showed no difference between healthy controls and patients with post-COVID dyspnea [
8], others have found exercise intolerance with evidence of circulatory and breathing pattern abnormalities [
9,
10]. There is similarly only limited understanding of the evolution of post-COVID dyspnea and associated outcomes over time, and it is difficult to predict the severity of long-term respiratory symptoms following recovery from the acute phase of COVID-19.
The aim of this study was to determine the prevalence, severity, and predictors of dyspnea at 12 months following hospitalization for COVID-19, and to describe the respiratory, cardiac, and patient-reported outcomes in patients with post-COVID dyspnea. These findings would help patients and clinicians better understand the heterogeneous causes of persistent post-COVID dyspnea such that more appropriate management approaches can be considered depending on the specific clinical scenario.
Discussion
This prospective cohort shows that dyspnea is a frequent symptom following COVID-19, and that most patients with dyspnea do not experience a meaningful improvement in the severity of their symptoms in the first year following infection. We also found that dyspnea was associated with worse sleep, mood, quality of life, and frailty in patients at 12 months post-COVID; however, there was no statistically significant difference in pulmonary function comparing dyspneic and non-dyspneic patients post-COVID. The severity of dyspnea and depressive symptoms at 3 months post-COVID were the only predictors of the severity of dyspnea at 12 months post-COVID. Together, these findings highlight the multifaceted nature of post-COVID dyspnea, with many patients having ongoing dyspnea for reasons other than overt pulmonary or cardiac consequences of COVID-19.
Mood may play a role in post-COVID dyspnea and can predict which patients are at risk for significant persistent dyspnea at 12 months. However, it is unclear whether dyspnea itself is driving these mood abnormalities, or whether the mood abnormality is instead contributing to the development of dyspnea. PTSD as a result of being hospitalized with COVID during a global pandemic may also be playing a role, as it is highly prevalent and associated with more persistent physical symptoms post-COVID [
24]. There is a trend towards DLCO being reduced in patients with significant dyspnea at 12 months post-COVID, suggesting a possible underlying persistent cardiopulmonary abnormality that may be contributing to the development of dyspnea in some patients. There is also heterogeneity in the dyspneic patients as some have solely reduced DLCO, while others have primarily mood abnormalities or combinations of PFT, cardiac, and mood abnormalities. Our findings emphasize that dyspnea in the post-COVID context is a complex sensory experience that may be influenced by mood in addition to possible underlying cardiopulmonary pathology, and there may be additional factors that are contributing. Previous studies have established decreased peripheral oxygen delivery and abnormal ventilatory response to aerobic activity as mechanisms of post-COVID dyspnea in the absence of cardiopulmonary limitations on invasive cardiopulmonary exercise testing [
9,
10]. Furthermore, based on our findings, the degree of contribution from these factors and the resulting severity of dyspnea appears to differ from patient to patient.
Post-COVID dyspnea was a persistent problem in our patient cohort, with 49% of patients hospitalized for acute COVID reporting no change in their dyspnea, 24% reporting an increase in their dyspnea, and 20% developing new-onset of clinically meaningful dyspnea at the 12-month mark when compared to 3 months post-COVID. The reason for the increase and new onset of dyspnea at the 12-month mark in a subset of patients is unclear but given the similar PFT findings in dyspneic and non-dyspneic patients, other suggested mechanisms may be implicated including changes in mood, peripheral oxygen delivery, and ventilatory response to aerobic activity over time [
9,
10,
24]. Furthermore, the morbidity associated with the dyspnea is also persistent, as evidenced by poorer outcomes in all patient-reported variables in those who had persistent dyspnea at 12 months. Interestingly, the severity of the acute infection does not appear to influence the degree of post-COVID dyspnea, as neither the need for ICU admission or for mechanical ventilation were associated with higher dyspnea scores. Previous studies on long term outcomes in patients with acute respiratory distress syndrome (ARDS) from various etiologies have also demonstrated similar prevalence of dyspnea and mood abnormalities as well as reduced DLCO at 12 months post-ARDS, but the study populations entirely consisted of patients who required mechanical ventilation [
25,
26]. We demonstrated similar long-term findings despite 82% of our patients not requiring mechanical ventilation and 51% not requiring ICU admission. This emphasizes the need to use standardized dyspnea and depression assessment tools, rather than traditional indicators like severity of illness or level of oxygen requirements, to identify patients who are at higher risk of post-COVID dyspnea given the multiple determinants of dyspnea beyond the degree of lung injury and resultant pulmonary pathology.
The persistent dyspnea and associated morbidity suggests potential benefit of using a validated dyspnea questionnaire at post-COVID follow-up visits, with similar rationale supporting utility of a standardized mood questionnaire. These can be applied in a variety of settings, including primary care clinics to both identify abnormalities and follow change over time, including potential response to intervention. Dyspnea and mood questionnaires could also be used at the time of discharge from hospital to determine who would benefit from outpatient follow-up and resources. Patients identified to have post-COVID dyspnea may benefit from early referral to supportive counselling and other psychiatric resources given the association of mood abnormalities with dyspnea. As well, dyspneic patients may also benefit from referral to pulmonary rehab, as previous literature demonstrates improvement in dyspnea and mood in the post-COVID patient population [
27].
Limitations of our study include the lack of baseline characteristics for the patients prior to the initial COVID-19 diagnosis. We attempted to account for any baseline cardiopulmonary abnormalities by performing a sensitivity analysis that excluded patients with known pre-existing cardiac or pulmonary disease, which yielded consistent findings to the analysis based on all included patients. Another limitation of our study is that newer variants of SARS‑CoV‑2 may result in varying prevalence and severity of post-COVID dyspnea compared to our study cohort compared to the α variant that was responsible for wave 1 infections. Vaccination may also influence the prevalence and severity of post-COVID dyspnea [
28,
29], which was not available at the time of initial infection. Thus, our results may not be generalizable to all post-COVID patient populations. Repeating this study in vaccinated and non-hospitalized post-COVID patients would help characterize post-COVID dyspnea in these populations.
In summary, post-COVID dyspnea is common, persistent, and has a significant impact on quality of life. Mood abnormalities may play a role in post-COVID dyspnea in addition to potential cardiorespiratory abnormalities. Dyspnea and depression at initial follow-up predict longer-term post-COVID dyspnea, emphasizing the need for standardized dyspnea and mood assessment following COVID-19 to identify patients at higher risk of post-COVID dyspnea and facilitate early and effective management.
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