Little is known about long-term sequelae of COVID-19.
To describe the consequences at 4 months in patients hospitalized for COVID-19.
In a prospective uncontrolled cohort study, survivors of COVID-19 ...who had been hospitalized in a university hospital in France between March 1 and May 29, 2020, underwent a telephone assessment 4 months after discharge, between July 15 and September 18, 2020. Patients with relevant symptoms and all patients hospitalized in an intensive care unit (ICU) were invited for further assessment at an ambulatory care visit.
Survival of hospitalization for COVID-19.
Respiratory, cognitive, and functional symptoms were assessed by telephone with the Q3PC cognitive screening questionnaire and a checklist of symptoms. At the ambulatory care visit, patients underwent pulmonary function tests, lung computed tomographic scan, psychometric and cognitive tests (including the 36-Item Short-Form Health Survey and 20-item Multidimensional Fatigue Inventory), and, for patients who had been hospitalized in the ICU or reported ongoing symptoms, echocardiography.
Among 834 eligible patients, 478 were evaluated by telephone (mean age, 61 years SD, 16 years; 201 men, 277 women). During the telephone interview, 244 patients (51%) declared at least 1 symptom that did not exist before COVID-19: fatigue in 31%, cognitive symptoms in 21%, and new-onset dyspnea in 16%. There was further evaluation in 177 patients (37%), including 97 of 142 former ICU patients. The median 20-item Multidimensional Fatigue Inventory score (n = 130) was 4.5 (interquartile range, 3.0-5.0) for reduced motivation and 3.7 (interquartile range, 3.0-4.5) for mental fatigue (possible range, 1 best to 5 worst). The median 36-Item Short-Form Health Survey score (n = 145) was 25 (interquartile range, 25.0-75.0) for the subscale "role limited owing to physical problems" (possible range, 0 best to 100 worst). Computed tomographic lung-scan abnormalities were found in 108 of 171 patients (63%), mainly subtle ground-glass opacities. Fibrotic lesions were observed in 33 of 171 patients (19%), involving less than 25% of parenchyma in all but 1 patient. Fibrotic lesions were observed in 19 of 49 survivors (39%) with acute respiratory distress syndrome. Among 94 former ICU patients, anxiety, depression, and posttraumatic symptoms were observed in 23%, 18%, and 7%, respectively. The left ventricular ejection fraction was less than 50% in 8 of 83 ICU patients (10%). New-onset chronic kidney disease was observed in 2 ICU patients. Serology was positive in 172 of 177 outpatients (97%).
Four months after hospitalization for COVID-19, a cohort of patients frequently reported symptoms not previously present, and lung-scan abnormalities were common among those who were tested. These findings are limited by the absence of a control group and of pre-COVID assessments in this cohort. Further research is needed to understand longer-term outcomes and whether these findings reflect associations with the disease.
Post-acute COVID-19 syndrome Montani, David; Savale, Laurent; Noel, Nicolas ...
European respiratory review,
03/2022, Volume:
31, Issue:
163
Journal Article
Peer reviewed
Open access
Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the coronavirus disease 2019 (COVID-19) pandemic that has resulted in millions of deaths and a major ...strain on health systems worldwide. Medical treatments for COVID-19 (anticoagulants, corticosteroids, anti-inflammatory drugs, oxygenation therapy and ventilation) and vaccination have improved patient outcomes. The majority of patients will recover spontaneously or after acute-phase management, but clinicians are now faced with long-term complications of COVID-19 including a large variety of symptoms, defined as "post-acute COVID-19 syndrome". Most studies have focused on patients hospitalised for severe COVID-19, but acute COVID-19 syndrome is not restricted to these patients and exists in outpatients. Given the diversity of symptoms and the high prevalence of persistent symptoms, the management of these patients requires a multidisciplinary team approach, which will result in the consumption of large amounts of health resources in the coming months. In this review, we discuss the presentation, prevalence, pathophysiology and evolution of respiratory complications and other organ-related injuries associated with post-acute COVID-19 syndrome.
Objectives
Whether COVID-19 leads to long-term pulmonary sequelae or not remains unknown. The aim of this study was to assess the prevalence of persisting radiological pulmonary fibrotic lesions in ...patients hospitalized for COVID-19.
Materials and methods
We conducted a prospective single-center study among patients hospitalized for COVID-19 between March and May 2020. Patients with residual symptoms or admitted into intensive care units were investigated 4 months after discharge by a chest CT (CCT) and pulmonary function tests (PFTs). The primary endpoint was the rate of persistent radiological fibrotic lesions after 4 months. Secondary endpoints included further CCT evaluation at 9 and 16 months, correlation of fibrotic lesions with clinical and PFT evaluation, and assessment of predictive factors.
Results
Among the 1151 patients hospitalized for COVID-19, 169 patients performed a CCT at 4 months. CCTs showed pulmonary fibrotic lesions in 19% of the patients (32/169). These lesions were persistent at 9 months and 16 months in 97% (29/30) and 95% of patients (18/19) respectively. There was no significant clinical difference based on dyspnea scale in patients with pulmonary fibrosis. However, PFT evaluation showed significantly decreased diffusing lung capacity for carbon monoxide (
p
< 0.001) and total lung capacity (
p
< 0.001) in patients with radiological lesions. In multivariate analysis, the predictive factors of radiological pulmonary fibrotic lesions were pulmonary embolism (OR = 9.0), high-flow oxygen (OR = 6.37), and mechanical ventilation (OR = 3.49).
Conclusion
At 4 months, 19% of patients investigated after hospitalization for COVID-19 had radiological pulmonary fibrotic lesions; they persisted up to 16 months.
Clinical relevance statement
Whether COVID-19 leads to long-term pulmonary sequelae or not remains unknown. The aim of this study was to assess the prevalence of persisting radiological pulmonary fibrotic lesions in patients hospitalized for COVID-19. The prevalence of persisting lesions after COVID-19 remains unclear. We assessed this prevalence and predictive factors leading to fibrotic lesions in a large cohort. The respiratory clinical impact of these lesions was also assessed.
Key Points
• Nineteen percent of patients hospitalized for COVID-19 had radiological fibrotic lesions at 4 months, remaining stable at 16 months.
• COVID-19 fibrotic lesions did not match any infiltrative lung disease pattern.
• COVID-19 fibrotic lesions were associated with pulmonary function test abnormalities but did not lead to clinical respiratory manifestation.
The NuA4 histone acetyltransferase complex is required for gene regulation, cell cycle progression, and DNA repair. Dissection of the 13‐subunit complex reveals that the Eaf7 subunit bridges Eaf5 ...with Eaf3, a H3K36me3‐binding chromodomain protein, and this Eaf5/7/3 trimer is anchored to NuA4 through Eaf5. This trimeric subcomplex represents a functional module, and a large portion exists in a native form outside the NuA4 complex. Gene‐specific and genome‐wide location analyses indicate that Eaf5/7/3 correlates with transcription activity and is enriched over the coding region. In agreement with a role in transcription elongation, the Eaf5/7/3 trimer interacts with phosphorylated RNA polymerase II and helps its progression. Loss of Eaf5/7/3 partially suppresses intragenic cryptic transcription arising in set2 mutants, supporting a role in nucleosome destabilization. On the other hand, loss of the trimer leads to an increase of replication‐independent histone exchange over the coding region of transcribed genes. Taken together, these results lead to a model where Eaf5/7/3 associates with elongating polymerase to promote the disruption of nucleosomes in its path, but also their refolding in its wake.
Synopsis
The multisubunit NuA4 complex is an essential gene regulatory acetyltransferase in yeast. Dissection of its subunits reveals a trimeric submodule independently associating with gene coding regions, which may act as a histone chaperone during RNA polymerase II transcriptional elongation.
Eaf5/7/3 forms a submodule within the NuA4 acetyltransferase complex and also functions as an independent native trimer.
High‐resolution genome‐wide analysis reveals NuA4 binding to promoters and coding regions of actively transcribed genes.
The Eaf5/7/3 trimer independently associates with the coding region of transcriptionally active genes and affects RNA polymerase II processivity.
Eaf5/7/3 interacts with phosphorylated, elongating RNA polymerase II and H3K36me3‐containing nucleosomes.
Eaf5/7/3 cooperates with FACT to promote transcription‐coupled nucleosomes disruption, as well as their refolding behind the polymerase to suppress histone exchange.
Dissection of the essential multisubunit NuA4 acetyltransferase reveals a trimeric subcomplex that interacts with elongating RNA polymerase II and functions independently to control transcription‐coupled histone exchange.
Dyspnoea is a common persistent symptom after COVID-19. Whether it is associated with functional respiratory disorders remains unclear.
We assessed the proportion and characteristics of patients with ..."functional respiratory complaints" (FRCs) (as defined by Nijmegen Questionnaire >22) among 177 post-COVID-19 individuals who benefited from outclinic evaluation in the COMEBAC study (
, symptomatic and/or intensive care unit (ICU) survivors at 4 months). In a distinct explanatory cohort of 21 consecutive individuals with unexplained post-COVID-19 dyspnoea after routine tests, we also analysed the physiological responses to incremental cardiopulmonary exercise testing (CPET).
In the COMEBAC cohort, 37 patients had significant FRCs (20.9%, IC95: 14.9-26.9). The prevalence of FRCs ranged from 7.2% (ICU patients) to 37.5% (non-ICU patients). The presence of FRCs was significantly associated with more severe dyspnoea, lower 6-min walk distance, more frequent psychological and neurological symptoms (cognitive complaint, anxiety, depression, insomnia and post-traumatic stress disorders) and poorer quality of life (all p<0.01). In the explanatory cohort, seven out of 21 patients had significant FRCs. Based on CPET, dysfunctional breathing was identified in 12 out of 21 patients, five out of 21 had normal CPET, three out of 21 had deconditioning and one out of 21 had evidence of uncontrolled cardiovascular disease.
FRCs are common during post-COVID-19 follow-up, especially among patients with unexplained dyspnoea. Diagnosis of dysfunctional breathing should be considered in those cases.
Cet article relate une expérience de conception d’espace public ayant fait l'objet d'une démarche participative complète de coconstruction : le projet Oasis à Chenôve (21). Est exposée la ...méthodologie définie pour mener à bien ce processus. Quelques moments significatifs dans la démarche de conception sont racontés afin de mettre en évidence des mécanismes d’idéation et de prise de décision collective. Les moments de bascule du projet : quand les temps de médiation et la manipulation des outils de participation (ou « objets intermédiaires ») conduisent à des petites révélations pour le public, le maître d’œuvre ou le maître d’ouvrage.
This article gives an account of the Oasis project in Chenôve (21), an experiment in the design of a public space which was the object of a totally participative approach. The methodology and some of ...the significant stages in the design process are related to highlight the mechanisms of ideation and collective decision-making which were adopted. Key stages in the project involved a mediation process and the use of participative tools (or "intermediary objects") which led to minor revelations for the public, the contractor and the contracting authority.
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