Dataset Information

Protein and cytokine profiles associated with COVID-19 disease severity in Puerto Rico

ABSTRACT: Viral strains, age, and host factors including genetics and proteins are associated with variable immune responses against SARS-CoV-2 and disease severity. We hypothesized that unique proteins/pathways are associated with COVID-19 disease severity in Puerto Rican Hispanics. A total of 121 men and women aged 21-80 years-old were recruited in Puerto Rico. Plasma samples were collected from unvaccinated COVID-19 infected subjects during acute disease (n=39) and compared to COVID-19 negative individuals (n=56) during acute disease using proteomics and cytokine expression. Infected individuals were stratified based on symptomatology as follows: mild (n=18), moderate (n=13), and severe (n=8). Quantitative proteomics was performed in plasma samples using Tandem Mass Tag (TMT) labeling. Cytokines in plasma were quantified using a human cytokine array. Proteomics analyses revealed 56 differentially regulated proteins and the top 3 pathways that were predicted to be inhibited in severe patients including LXR/RXR signaling, Production of NO and ROS in macrophages, and Synaptogenesis signaling. Decreased cadherin-13 validated by ELISA, which participates in synaptogenesis, is a novel protein is a novel protein not previously reported in other studies of COVID-19 severity and validated by ELISA. Cytokine analyses showed that TNF⍺ levels decreased with disease severity. This study uncovers potential host predictors of COVID-19 severity and new avenues for treatment in Puerto Rican Hispanics.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Cell, Blood Plasma

DISEASE(S): Covid-19

SUBMITTER: Loyda Melendez

LAB HEAD: Loyda Melendez

PROVIDER: PXD046103 | Pride | 2024-06-16

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	TMT_Analysis_COVID-19_EX2_20Dic2021_rev.msf	Msf
	TMT_Analysis_COVID-19_EX2_20Dic2021_rev.mzML	Mzml
	TMT_Analysis_COVID-19_EX2_20Dic2021_rev.mzid.gz	Mzid
	TMT_Pool1A_Fraction1_COVID19_Exp2_9nov2021.raw	Raw
	TMT_Pool1A_Fraction2_COVID19_Exp2_9nov2021.raw	Raw

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Publications

Plasma Proteins Associated with COVID-19 Severity in Puerto Rico.

Rosario-Rodríguez Lester J LJ Cantres-Rosario Yadira M YM Carrasquillo-Carrión Kelvin K Rosa-Díaz Alexandra A Rodríguez-De Jesús Ana E AE Rivera-Nieves Verónica V Tosado-Rodríguez Eduardo L EL Méndez Loyda B LB Roche-Lima Abiel A Bertrán Jorge J Meléndez Loyda M LM

International journal of molecular sciences 20240516 10

Viral strains, age, and host factors are associated with variable immune responses against SARS-CoV-2 and disease severity. Puerto Ricans have a genetic mixture of races: European, African, and Native American. We hypothesized that unique host proteins/pathways are associated with COVID-19 disease severity in Puerto Rico. Following IRB approval, a total of 95 unvaccinated men and women aged 21-71 years old were recruited in Puerto Rico from 2020-2021. Plasma samples were collected from COVID-19- ...[more]

PMID: 38791465

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Project description:Background. COVID-19-induced neurological disease is a growing concern. Here we provide a comprehensive clinical, molecular, and neuroimaging investigation of patients presenting neurological symptoms to investigate underlying processes. Methods. We performed a detailed systematized clinical, laboratory, and neuroimaging (CT/MRI) data analysis from 35 mild to severe Brazilian COVID-19 hospitalised patients with clinical indications for cerebrospinal fluid (CSF) exam. In patients' CSF, we measured interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-α) and the Alzheimer's disease-associated biomarkers amyloid-beta (Aβ)1-40, Aβ1-42, Tau and pTau181 levels (n=31-35). In addition, CSF proteomics and the search for SARS-CoV-2 spike protein presence using shotgun and targeted multiple reaction monitoring liquid-chromatography/mass-spectrometry were performed (n=16). We further evaluated a 29-cytokine panel in patients’ blood (n=16). An electronic questionnaire was conducted one-year post-hospitalisation (n=19, 63.3%). Findings. COVID-19 patients presented heterogeneous clinical and neurological features, including encephalopathy, encephalitis, and neuromuscular syndromes, despite low pulmonary burden. Patients showed increased circulating cytokines and CSF IL-6 and TNF-α levels compared to controls. Alzheimer’s disease-related biomarkers were unaltered compared to controls. COVID-19 altered CSF proteomic pathways associated to complement and coagulation cascades, immune-inflammatory, metabolism and amyloidosis. We found no traces of spike protein in patients’ CSF. Severe patients presented more pronounced neuroimaging alterations, altered CSF levels of IL-6, Tau, and Aβ-species compared to mild patients. Peripheral inflammation markers correlated with CSF IL-6 and Tau-species levels. Finally, in a one-year post-COVID survey, survivors were not recovered entirely (12/19) and reported confusion or memory/attention deficits (13/19). Interpretation. COVID-19 induces a broad spectrum of neurological presentations associated with changes in central nervous system (CNS) inflammatory and neurodegenerative molecular and structural biomarkers that correlate with systemic inflammation and disease severity. Given that neurological symptoms persist up to one-year post-COVID, our results urge us to investigate whether systemic, and CNS molecular changes are permanent or alleviated so that COVID-19 patients with lingering symptoms are adequately treated.