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1.
researchsquare; 2021.
Preprint in English | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-387067.v1

ABSTRACT

Background: The occurrence of post-intensive care syndrome (PICS) in critically ill patients with coronavirus disease (COVID-19) remains unclear. This study aimed to investigate the physical, mental, and cognitive components of PICS in intensive care unit (ICU)-treated COVID-19 survivors. Methods: : This prospective cohort study enrolled patients with COVID-19 who were treated in the ICU of a single institution between March 19, 2020 and April 30, 2020. A survey was sent by postal mail at 4 and 6 months after ICU discharge. The questionnaire comprised the post-COVID-19 functional status (PCFS) scale and the modified medical research council dyspnea scale (mMRC) for assessing physical PICS; the impact of event scale-revised (IES-R) and the hospital anxiety and depression scale (HADS) for assessing mental PICS; and self-assessment questions for concentration, memory, and forgetfulness for assessing cognitive PICS. Physical PICS was defined by a PCFS or mMRC score ≥1. Mental PICS was defined by an IES-R score ≥25 or if the HADS score for anxiety or depression components was ≥8. Cognitive PICS was defined according to patient complaints of deterioration in concentration, memory, or forgetfulness. The primary outcome was PICS occurrence at 4 months. Moreover, we assessed the co-occurrence of the three PICS components. Results: : Twenty patients consented to participate in the study and responded to the survey. The median age was 57.5 years, and 80% of the patients were male; moreover, 50%, 55%, and 80% lived alone, were married, and were employed/self-employed before hospitalization, respectively. During ICU stay, 80%, 75%, and 25% received invasive mechanical ventilation, systemic steroids, and continuous benzodiazepine, respectively. Delirium occurred in 40% of patients. The median days of ICU and hospital stay were 6 and 21, respectively. Physical, mental, and cognitive PICS occurred in 14 (78%), 9 (45%), and 11 (55%) patients, respectively. There were 16 (80%) and 8 (40%) patients with at least one and all PICS components, respectively. Conclusions: : Our findings revealed a high rate of PICS in COVID-19 survivors. Long-term and comprehensive evaluation of all three PICS components is crucial for providing appropriate care to these patients.


Subject(s)
Coronavirus Infections , Anxiety Disorders , Ichthyosis, X-Linked , Dyspnea , Intellectual Disability , COVID-19
2.
ssrn; 2020.
Preprint in English | PREPRINT-SSRN | ID: ppzbmed-10.2139.ssrn.3641894

ABSTRACT

The current COVID-19 pandemic is caused by the SARS-CoV-2 betacoronavirus, which utilizes its highly glycosylated trimeric Spike protein to bind to the cell surface receptor ACE2 glycoprotein and facilitate host cell entry.  We utilized glycomics-informed glycoproteomics to characterize site-specific microheterogeneity of glycosylation for a recombinant trimer Spike mimetic immunogen and for a soluble version of human ACE2.  We combined this information with bioinformatic analyses of natural variants and with existing 3D-structures of both glycoproteins to generate molecular dynamics simulations of each glycoprotein alone and interacting with one another.  Our results highlight roles for glycans in sterically masking polypeptide epitopes and directly modulating Spike-ACE2 interactions.  Furthermore, our results illustrate the impact of viral evolution and divergence on Spike glycosylation, as well as the influence of natural variants on ACE2 receptor glycosylation that, taken together, can facilitate immunogen design to achieve antibody neutralization and inform therapeutic strategies to inhibit viral infection.


Subject(s)
COVID-19
3.
biorxiv; 2020.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2020.06.25.172403

ABSTRACT

The current COVID-19 pandemic is caused by the SARS-CoV-2 betacoronavirus, which utilizes its highly glycosylated trimeric Spike protein to bind to the cell surface receptor ACE2 glycoprotein and facilitate host cell entry. We utilized glycomics-informed glycoproteomics to characterize site-specific microheterogeneity of glycosylation for a recombinant trimer Spike mimetic immunogen and for a soluble version of human ACE2. We combined this information with bioinformatic analyses of natural variants and with existing 3D-structures of both glycoproteins to generate molecular dynamics simulations of each glycoprotein alone and interacting with one another. Our results highlight roles for glycans in sterically masking polypeptide epitopes and directly modulating Spike-ACE2 interactions. Furthermore, our results illustrate the impact of viral evolution and divergence on Spike glycosylation, as well as the influence of natural variants on ACE2 receptor glycosylation that, taken together, can facilitate immunogen design to achieve antibody neutralization and inform therapeutic strategies to inhibit viral infection.


Subject(s)
Virus Diseases , COVID-19
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