Surviving Critical Care: A Follow-Up Study Assessing Pulmonary Function, Cardiopulmonary Exercise Testing, and Quality of Life in COVID-19-Affected Patients.
Survivors of severe COVID-19 face complex challenges and a high degree of pulmonary sequelae. Therefore, we aim to describe their ongoing health burden.
In this single-center prospective cohort study, COVID-19 ICU survivors were invited 3 and 6 months after ICU discharge. We examined pulmonary function with pulmonary function tests (PFT) and cardiopulmonary exercise testing (CPET), and we established health-related quality of life (HRQL) and health status (HS) with the EuroQol five-dimension five-level (EQ-5D-5L), the short-form health survey 12 (SF-12), and the modified British Medical Research Council dyspnea scale (mMRC) questionnaires.
Out of the 53 individuals screened, 23 participated in this study. Throughout both assessment points, participants maintained PFT results within range, apart from a decline in the transfer factor of the lung for carbon monoxide (TLCO). CPET showed improved fitness but persistent ventilatory deficiencies, indicated by altered dead space ventilation (VD/VT) and elevated arterial-alveoli gradient for oxygen (AaDO2). HRQL and HS remained compromised, with both physical (PCS) and mental component summary (MCS) scores significantly lower than the standardized norm population scores. Also, there was a rise in the prevalence of issues related to mobility, pain/discomfort, and anxiety/depression, and an increase in reported dyspnea.
These results enhance our comprehension of the complex difficulties faced by COVID-19 ICU survivors. Six months post-discharge, CPET revealed the presence of ventilatory insufficiencies. Additionally, there was a decline in HRQL and HS, notably affected by mental health concerns and an increase in the level of dyspnea.
Engel L
，Strassmann S
，Merten M
，Schaefer S
，Färber J
，Windisch W
，Karagiannidis C
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Persistent symptoms and clinical findings in adults with post-acute sequelae of COVID-19/post-COVID-19 syndrome in the second year after acute infection: A population-based, nested case-control study.
Self-reported health problems following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are common and often include relatively non-specific complaints such as fatigue, exertional dyspnoea, concentration or memory disturbance and sleep problems. The long-term prognosis of such post-acute sequelae of COVID-19/post-COVID-19 syndrome (PCS) is unknown, and data finding and correlating organ dysfunction and pathology with self-reported symptoms in patients with non-recovery from PCS is scarce. We wanted to describe clinical characteristics and diagnostic findings among patients with PCS persisting for >1 year and assessed risk factors for PCS persistence versus improvement.
This nested population-based case-control study included subjects with PCS aged 18-65 years with (n = 982) and age- and sex-matched control subjects without PCS (n = 576) according to an earlier population-based questionnaire study (6-12 months after acute infection, phase 1) consenting to provide follow-up information and to undergo comprehensive outpatient assessment, including neurocognitive, cardiopulmonary exercise, and laboratory testing in four university health centres in southwestern Germany (phase 2, another 8.5 months [median, range 3-14 months] after phase 1). The mean age of the participants was 48 years, and 65% were female. At phase 2, 67.6% of the patients with PCS at phase 1 developed persistent PCS, whereas 78.5% of the recovered participants remained free of health problems related to PCS. Improvement among patients with earlier PCS was associated with mild acute index infection, previous full-time employment, educational status, and no specialist consultation and not attending a rehabilitation programme. The development of new symptoms related to PCS among participants initially recovered was associated with an intercurrent secondary SARS-CoV-2 infection and educational status. Patients with persistent PCS were less frequently never smokers (61.2% versus 75.7%), more often obese (30.2% versus 12.4%) with higher mean values for body mass index (BMI) and body fat, and had lower educational status (university entrance qualification 38.7% versus 61.5%) than participants with continued recovery. Fatigue/exhaustion, neurocognitive disturbance, chest symptoms/breathlessness and anxiety/depression/sleep problems remained the predominant symptom clusters. Exercise intolerance with post-exertional malaise (PEM) for >14 h and symptoms compatible with myalgic encephalomyelitis/chronic fatigue syndrome were reported by 35.6% and 11.6% of participants with persistent PCS patients, respectively. In analyses adjusted for sex-age class combinations, study centre and university entrance qualification, significant differences between participants with persistent PCS versus those with continued recovery were observed for performance in three different neurocognitive tests, scores for perceived stress, subjective cognitive disturbances, dysautonomia, depression and anxiety, sleep quality, fatigue and quality of life. In persistent PCS, handgrip strength (40.2 [95% confidence interval (CI) [39.4, 41.1]] versus 42.5 [95% CI [41.5, 43.6]] kg), maximal oxygen consumption (27.9 [95% CI [27.3, 28.4]] versus 31.0 [95% CI [30.3, 31.6]] ml/min/kg body weight) and ventilatory efficiency (minute ventilation/carbon dioxide production slope, 28.8 [95% CI [28.3, 29.2]] versus 27.1 [95% CI [26.6, 27.7]]) were significantly reduced relative to the control group of participants with continued recovery after adjustment for sex-age class combinations, study centre, education, BMI, smoking status and use of beta blocking agents. There were no differences in measures of systolic and diastolic cardiac function at rest, in the level of N-terminal brain natriuretic peptide blood levels or other laboratory measurements (including complement activity, markers of Epstein-Barr virus [EBV] reactivation, inflammatory and coagulation markers, serum levels of cortisol, adrenocorticotropic hormone and dehydroepiandrosterone sulfate). Screening for viral persistence (PCR in stool samples and SARS-CoV-2 spike antigen levels in plasma) in a subgroup of the patients with persistent PCS was negative. Sensitivity analyses (pre-existing illness/comorbidity, obesity, medical care of the index acute infection) revealed similar findings. Patients with persistent PCS and PEM reported more pain symptoms and had worse results in almost all tests. A limitation was that we had no objective information on exercise capacity and cognition before acute infection. In addition, we did not include patients unable to attend the outpatient clinic for whatever reason including severe illness, immobility or social deprivation or exclusion.
In this study, we observed that the majority of working age patients with PCS did not recover in the second year of their illness. Patterns of reported symptoms remained essentially similar, non-specific and dominated by fatigue, exercise intolerance and cognitive complaints. Despite objective signs of cognitive deficits and reduced exercise capacity, there was no major pathology in laboratory investigations, and our findings do not support viral persistence, EBV reactivation, adrenal insufficiency or increased complement turnover as pathophysiologically relevant for persistent PCS. A history of PEM was associated with more severe symptoms and more objective signs of disease and might help stratify cases for disease severity.
Peter RS
，Nieters A
，Göpel S
，Merle U
，Steinacker JM
，Deibert P
，Friedmann-Bette B
，Nieß A
，Müller B
，Schilling C
，Erz G
，Giesen R
，Götz V
，Keller K
，Maier P
，Matits L
，Parthé S
，Rehm M
，Schellenberg J
，Schempf U
，Zhu M
，Kräusslich HG
，Rothenbacher D
，Kern WV
，EPILOC Phase 2 Study Group
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Characterization of postintensive care syndrome in a prospective cohort of survivors of COVID-19 critical illness: a 12-month follow-up study.
Studies integrating an exhaustive longitudinal long-term follow-up of postintensive care syndrome (PICS) in critically ill COVID-19 survivors are scarce. We aimed to 1) describe PICS-related sequelae over a 12-month period after intensive care unit (ICU) discharge, 2) identify relevant demographic and clinical factors related to PICS, and 3) explore how PICS-related sequelae may influence health-related quality of life (HRQoL) in critically ill COVID-19 survivors.
We conducted a prospective cohort study in adult critically ill survivors of SARS-CoV-2 infection that did or did not need invasive mechanical ventilation (IMV) during the COVID-19 pandemic in Spain (March 2020 to January 2021). We performed a telemedicine follow-up of PICS-related sequelae (physical/functional, cognitive, and mental health) and HRQoL with five data collection points. We retrospectively collected demographic and clinical data. We used multivariable mixed-effects models for data analysis.
We included 142 study participants in the final analysis, with a median [interquartile range] age of 61 [53-68] yr; 35% were female and 59% needed IMV. Fatigue/dyspnea, pain, impaired muscle function, psychiatric symptomatology and reduced physical HRQoL were prominent sequelae early after ICU discharge. Over the 12-month follow-up, functionality and fatigue/dyspnea improved progressively, while pain remained stable. We observed slight fluctuations in anxiety symptoms and perception of cognitive deficit, whereas posttraumatic stress disorder (PTSD) and depressive symptoms improved, with a mild rebound at the end of the follow-up. Female sex, younger age, and the need for IMV were risk factors for PICS, while having higher cognitive reserve was a potential protective factor. Physical HRQoL scores showed a general improvement over time, whereas mental HRQoL remained stable. Shorter ICU stay, better functionality, and lower scores for fatigue/dyspnea and pain were associated with better physical HRQoL, while lower scores for anxiety, depression, and PTSD were associated with better mental HRQoL.
Postintensive care syndrome was common in COVID-19 critical illness survivors and persisted in a significant proportion of patients one year after ICU discharge, impacting HRQoL. The presence of risk factors for PICS may identify patients who are more likely to develop the condition and who would benefit from more specific and closer follow-up after ICU admission.
ClinicalTrials.gov ( NCT04422444 ); first submitted 9 June 2020.
Fernández-Gonzalo S
，Navarra-Ventura G
，Gomà G
，Godoy-González M
，Oliveras L
，Ridao Sais N
，Espinal C
，Fortià C
，De Haro C
，Ochagavía A
，Jodar M
，Forné C
，Santos-Pulpon V
，Sarlabous L
，Bacardit N
，Subirà C
，Fernández R
，Palao D
，Roca O
，Blanch L
，López-Aguilar J
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Chest CT Findings at Six Months Following COVID-19 ARDS - Correlation With the mMRC Dyspnea Scale and Pulmonary Function Tests.
Background: Many survivors of severe COVID-19 pneumonia experience lingering respiratory issues. There is limited research on follow-up chest imaging findings in patients with COVID-19 ARDS, particularly in relation to their mMRC dyspnea scores and pulmonary function tests (PFTs). This study addresses this gap by investigating the clinical characteristics, mMRC dyspnea scores, PFTs, and chest CT findings of COVID-19 ARDS patients at the 6 months post-recovery. By analyzing these variables together, we aim to gain a better understanding of the long-term health consequences of COVID-19 ARDS. Methods: This prospective observational study included 56 subjects with COVID-19 ARDS with dyspnea at the six-month follow-up visits. These patients were evaluated by chest CT, mMRC dyspnea scale, and PFT. The CT severity score was calculated individually for each of the four major imaging findings - ground glass opacities (GGOs), parenchymal/atelectatic bands, reticulations/septal thickening, and consolidation - using a modified CT severity scoring system. Statistics were carried out to find any association between individual CT chest findings and the mMRC dyspnea scale and forced vital capacity (FVC). p values < 0.05 were considered statistically significant. Results: Our study population had a mean age of 55.86 ± 9.60 years, with 44 (78.6%) being men. Grades 1, 2, 3, and 4 on the mMRC dyspnea scale were seen in 57.1%, 30.4%, 10.7%, and 1.8% of patients respectively. Common CT findings observed were GGOs (94.6%), reticulations/septal thickening (96.4%), parenchymal/atelectatic bands (92.8%), and consolidation (14.3%). The mean modified CT severity scores for GGOs, reticulations/septal thickening, parenchymal/atelectatic bands, and consolidation were 10.32 ± 5.51 (range: 0-21), 7.66 ± 4.33 (range: 0-19), 4.77 ± 3.03 (range: 0-14) and 0.29 ± 0.91 (range 0-5) respectively. Reticulations/septal thickening (p = 0.0129) and parenchymal/atelectatic bands (p = 0.0453) were associated with an increased mMRC dyspnea scale. Parenchymal/atelectatic bands were also associated with abnormal FVC (<80%) (p = 0.0233). Conclusion: Six-month follow-up chest CTs of COVID-19 ARDS survivors with persistent respiratory problems showed a statistically significant relationship between increased mMRC dyspnea score and imaging patterns of reticulations/septal thickening and parenchymal/atelectatic bands; while parenchymal/atelectatic bands also showed a statistically significant correlation with reduced FVC.
Garg M
，Prabhakar N
，Devkota S
，Dhooria S
，Debi U
，Dua A
，Singh T
，Malarakunte M
，Bhatia H
，Sandhu MS
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