Factors associated with phenotypes of dyspnea in post-COVID-19 condition: a cross-sectional study.

Post-COVID-19 condition (PCC) is defined as the persistence of symptoms, like fatigue and dyspnea, at least 3 months post-COVID infection. As dyspnea is a common symptom, we attempted to further clinically phenotype those with PCC-associated dyspnea. 1642 adults (average age of 49.6y with 63% female-predominance and BMI of 31.2 kg/m2) with physician confirmed diagnosis of PCC from June 2020-April 2023 in Alberta, Canada were included. Those with dyspnea were more likely to be female (56.5%, p = 0.005) and have higher BMI (31.3 kg/m2 vs. 29.5 kg/m2; p = 0.0008), history of asthma (21.1% vs. 12.3%; p < 0.001), more persistent PCC symptoms (p = 0.0001), more functional limitations, as well as lower quality of life (p < 0.0001). Multivariable-adjusted logistic regression analysis demonstrated dyspnea was independently associated with fatigue (OR = 4.20; CI = 2.71,6.59) and inversely associated with hospitalization for COVID-19 (OR = 0.53; CI = 0.32,0.91), age (OR = 0.98 per one year of age; CI = 0.96,0.99) and 6-min-walk-distance per 10 m difference (OR = 0.98, CI = 0.96,1.0). Fatigue was a predictor of dyspnea, and was associated with milder infection, higher BMI, and reduced 6-min-walk-distance despite normal pulmonary function. Reduced TLC or DLCO was associated with more severe infection and reduced 6-min-walk-distance. Thus, we speculate there are at least two dyspnea-associated phenotypes: phenotype with pronounced fatigue (normal PFT) and phenotype with pronounced pulmonary abnormalities (abnormal PFT). Improved understanding of the dyspnea-associated phenotypes may allow for better targeted rehabilitation.

Characterizing long-COVID brain fog: a retrospective cohort study.

BACKGROUND: Long COVID or post-COVID condition (PCC) is a common complication following acute COVID-19 infection. PCC is a multi-systems disease with neurocognitive impairment frequently reported regardless of age. Little is known about the risk factors, associated biomarkers and clinical trajectory of patients with this symptom. OBJECTIVE: To determine differences in clinical risk factors, associated biochemical markers and longitudinal clinical trajectories between patients with PCC with subjective neurocognitive symptoms (NC+) or without (NC-). METHODS: A retrospective longitudinal cohort study was performed using a well-characterized provincial database of patients with clinically confirmed PCC separated into NC+ and NC- cohorts. Demographical, clinical and biochemical differences at initial consultation between the two patient cohorts were analyzed in cross-section. Multivariate regression analyses were conducted to identify independent risk factors for neurocognitive impairment. Determination of the recovery trajectory was performed using serial assessments of the patient-reported health-related quality of life (HR-QoL) metric Eq-5D-5L-vas score. FINDINGS: Women, milder acute infection and pre-existing mental health diagnoses were independently associated with subjective neurocognitive impairment at 8 months post-infection. NC + patients demonstrated lower levels of IgG, IgG1 and IgG3 compared to NC- patients. The NC + cohort had poorer HR-QoL at initial consultation 8 months post-infection with gradual improvement over 20 months post-infection. CONCLUSIONS: Neurocognitive impairment represents a severe phenotype of PCC, associated with unique risk factors, aberrancy in immune response and a delayed recovery trajectory. Those with risk factors for neurocognitive impairment can be identified early in the disease trajectory for more intense medical follow-up.

Reliability and validity of the post COVID-19 condition stigma questionnaire: A prospective cohort study.

Background: Many of the 10-20% percent of COVID-19 survivors who develop Post COVID-19 Condition (PCC, or Long COVID) describe experiences suggestive of stigmatization, a known social determinant of health. Our objective was to develop an instrument, the Post COVID-19 Condition Stigma Questionnaire (PCCSQ), with which to quantify and characterise PCC-related stigma. Methods: We conducted a prospective cohort study to assess the reliability and validity of the PCCSQ. Patients referred to our Post COVID-19 Clinic in the Canadian City of Edmonton, Alberta between May 29, 2021 and May 24, 2022 who met inclusion criteria (attending an academic post COVID-19 clinic; age ≥18 years; persistent symptoms and impairment at ≥ 12 weeks since PCR positive acute COVID-19 infection; English-speaking; internet access; consenting) were invited to complete online questionnaires, including the PCCSQ. Analyses were conducted to estimate the instrument's reliability, construct validity, and association with relevant instruments and defined health outcomes. Findings: Of the 198 patients invited, 145 (73%) met inclusion criteria and completed usable questionnaires. Total Stigma Score (TSS) on the PCCSQ ranged from 40 to 174/200. The mean (SD) was 103.9 (31.3). Cronbach's alpha was 0.97. Test-retest reliability was 0.92. Factor analysis supported a 6-factor latent construct. Subtest reliabilities were >0.75. Individuals reporting increased TSS occurred across all demographic groups. Increased risk categories included women, white ethnicity, and limited educational opportunities. TSS was positively correlated with symptoms, depression, anxiety, loneliness, reduced self-esteem, thoughts of self-harm, post-COVID functional status, frailty, EQ5D5L score, and number of ED visits. It was negatively correlated with perceived social support, 6-min walk distance, and EQ5D5L global rating. Stigma scores were significantly increased among participants reporting employment status as disabled. Interpretation: Our findings suggested that the PCCSQ is a valid, reliable tool with which to estimate PCC-related stigma. It allows for the identification of patients reporting increased stigma and offers insights into their experiences. Funding: The Edmonton Post COVID-19 Clinic is supported by the University of Alberta and Alberta Health Services. No additional sources of funding were involved in the execution of this research study.

Persistent dyspnea after COVID-19 is not related to cardiopulmonary impairment; a cross-sectional study of persistently dyspneic COVID-19, non-dyspneic COVID-19 and controls.

Background: Up to 53% of individuals who had mild COVID-19 experience symptoms for >3-month following infection (Long-CoV). Dyspnea is reported in 60% of Long-CoV cases and may be secondary to impaired exercise capacity (VO2peak) as a result of pulmonary, pulmonary vascular, or cardiac insult. This study examined whether cardiopulmonary mechanisms could explain exertional dyspnea in Long-CoV. Methods: A cross-sectional study of participants with Long-CoV (n = 28, age 40 ± 11 years, 214 ± 85 days post-infection) and age- sex- and body mass index-matched COVID-19 naïve controls (Con, n = 24, age 41 ± 12 years) and participants fully recovered from COVID-19 (ns-CoV, n = 14, age 37 ± 9 years, 198 ± 89 days post-infection) was conducted. Participants self-reported symptoms and baseline dyspnea (modified Medical Research Council, mMRC, dyspnea grade), then underwent a comprehensive pulmonary function test, cardiopulmonary exercise test, exercise pulmonary diffusing capacity measurement, and rest and exercise echocardiography. Results: VO2peak, pulmonary function and cardiac/pulmonary vascular parameters were not impaired in Long- or ns-CoV compared to normative values (VO2peak: 106 ± 25 and 107 ± 25%predicted, respectively) and cardiopulmonary responses to exercise were otherwise normal. When Long-CoV were stratified by clinical dyspnea severity (mMRC = 0 vs mMRC≥1), there were no between-group differences in VO2peak. During submaximal exercise, dyspnea and ventilation were increased in the mMRC≥1 group, despite normal operating lung volumes, arterial saturation, diffusing capacity and indicators of pulmonary vascular pressures. Interpretation: Persistent dyspnea after COVID-19 was not associated with overt cardiopulmonary impairment or exercise intolerance. Interventions focusing on dyspnea management may be appropriate for Long-CoV patients who report dyspnea without cardiopulmonary impairment.

The effectiveness of pulmonary rehabilitation for Post-COVID symptoms: A rapid review of the literature.

BACKGROUND: Multi-disciplinary rehabilitation is recommended for individuals with post-acute sequelae of COVID-19 infection (i.e., symptoms 3-4 weeks after acute infection). There are emerging reports of use of pulmonary rehabilitation (PR) in the post-acute stages of COVID-19, however the appropriateness of PR for managing post-COVID symptoms remains unclear. To offer practical guidance with regards to post-COVID PR, a greater understanding of the clinical effectiveness literature is required. METHODS: A rapid review of the published literature was completed. An electronic database search of the literature published between July 1, 2020 and June 1, 2021 was performed in MEDLINE, Pubmed, and EMBASE. Primary studies evaluating the clinical effectiveness of PR for individuals with post-COVID symptoms were included. RESULTS: Nine studies evaluating the effectiveness of PR were identified; most were small, experimental or quasi-experimental studies, including 1 RCT, and were primarily of low quality. After attending PR, all studies reported improvements in exercise capacity, pulmonary function, and/or quality of life for individuals with post-COVID symptoms who had been hospitalized for their acute COVID-19 infection. Few studies evaluated changes in post-COVID symptom severity or frequency and, of these, improvements in dyspnea, fatigue, anxiety and depression were observed following PR. Further, no studies evaluated non-hospitalized patients or long-term outcomes beyond 3 months after initiating PR. CONCLUSIONS: With limited high-quality evidence, any recommendations or practical guidance for PR programmes for those with post-COVID symptoms should consider factors such as feasibility, current PR capacity, and resource constraints.

COVID-19 hospitalization is associated with pulmonary/diffusion abnormalities but not post-acute sequelae of COVID-19 severity.

Coronavirus disease-19 (COVID-19) has resulted in much acute morbidity and mortality worldwide. There is now a growing recognition of the post-acute sequela of COVID-19, termed long COVID. However, the risk factors contributing to this condition remain unclear. Here, we address the growing controversy in the literature of whether hospitalization is a risk factor for long COVID. We found that hospitalization is associated with worse pulmonary restriction and reduction in diffusion capacity at 3 months post-infection. However, the impact on mental health, functional and quality of life is equally severe in those who have and have not been hospitalized during the acute infection. These findings suggest that hospitalization is a risk factor for pulmonary complications of long COVID but not the overall severity of long COVID.

Exertional intolerance and dyspnea with preserved lung function: an emerging long COVID phenotype?

The COVID-19 pandemic has resulted in significant acute morbidity and mortality worldwide. There is now a growing recognition of the longer-term sequelae of this infection, termed "long COVID". However, little is known about this condition. Here, we describe a distinct phenotype seen in a subset of patients with long COVID who have reduced exercise tolerance as measured by the 6 min walk test. They are associated with significant exertional dyspnea, reduced health-related quality of life and poor functional status. However, surprisingly, they do not appear to have any major pulmonary function abnormalities or increased burden of neurologic, musculoskeletal or fatigue symptoms.

Assessing Symptoms, Concerns, and Quality of Life in Noncancer Patients at End of Life: How Concordant Are Patients and Family Proxy Members?

CONTEXT: It has become commonplace to use family caregivers as proxy responders where patients are unable to provide information about their symptoms and concerns to health care providers. OBJECTIVES: The objective of this study was to determine the degree of concordance between patients' and family members' reports of patient symptoms and concerns at end of life. METHODS: Sample dyads included a mix of patients residing at home, in a nursing home, in a long-term care facility, or in hospice. Diagnoses included patients with amyotrophic lateral sclerosis (n = 75), chronic obstructive pulmonary disease (n = 52), end-stage renal disease (n = 42), and institutionalized, cognitively intact frail elderly (n = 49). Dyads completed the Patient Dignity Inventory (PDI), the modified Structured Interview Assessment of Symptoms and Concerns in Palliative Care, and Graham and Longman's two-item Quality of Life Scale. RESULTS: Concordance was less than 70% for seven of the 25 PDI items, with the lowest concordance (65.1%) for the item "not being able to continue with my usual routines." For all but one PDI item, discordance was in the direction of family members reporting that the patient was worse off than the patient had indicated. Where discordance was observed on the Structured Interview Assessment of Symptoms and Concerns in Palliative Care and Quality of Life Scales, the trend toward family members overreporting patient distress and poor quality of life continued. CONCLUSION: Understanding discordance between patients and family member reports of symptoms and concerns is a valuable step toward minimizing patient and family burden at end of life.

Correction: Dignity and Distress towards the End of Life across Four Non-Cancer Populations.

[This corrects the article DOI: 10.1371/journal.pone.0147607.].

Dignity and Distress towards the End of Life across Four Non-Cancer Populations.

OBJECTIVE: The purpose of this study was to identify four non-cancer populations that might benefit from a palliative approach; and describe and compare the prevalence and patterns of dignity related distress across these diverse clinical populations. DESIGN: A prospective, multi-site approach was used. SETTING: Outpatient clinics, inpatient facilities or personal care homes, located in Winnipeg, Manitoba and Edmonton, Alberta, Canada. PARTICIPANTS: Patients with advanced Amyotrophic Lateral Sclerosis (ALS), Chronic Obstructive Pulmonary Disease (COPD), End Stage Renal Disease (ESRD); and the institutionalized alert frail elderly. MAIN OUTCOME MEASURE: In addition to standardized measures of physical, psychological and spiritual aspects of patient experience, the Patient Dignity Inventory (PDI). RESULTS: Between February 2009 and December 2012, 404 participants were recruited (ALS, 101; COPD, 100; ESRD, 101; and frail elderly, 102). Depending on group designation, 35% to 58% died within one year of taking part in the study. While moderate to severe loss of sense of dignity did not differ significantly across the four study populations (4-11%), the number of PDI items reported as problematic was significantly different i.e. ALS 6.2 (5.2), COPD 5.6 (5.9), frail elderly 3.0 (4.4) and ESRD 2.3 (3.9) [p < .0001]. Each of the study populations also revealed unique and distinct patterns of physical, psychological and existential distress. CONCLUSION: People with ALS, COPD, ESRD and the frail elderly face unique challenges as they move towards the end of life. Knowing the intricacies of distress and how they differ across these groups broadens our understanding of end-of-life experience within non-cancer populations and how best to meet their palliative care needs.