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Cardiovascular symptoms of PASC are associated with trace-level circulatory cytokines that affect the function of primary human cardiomyocytes

ABSTRACT: Globally, over 65 million individuals are estimated to suffer from post-acute sequelae of COVID-19 (PASC). A large number of individuals living with PASC experience cardiovascular symptoms (i.e. chest pain and heart palpitations) (PASC-CVS). The role of chronic inflammation in these symptoms, in particular in individuals with symptoms persisting for >1 year after SARS-CoV-2 infection, remains to be determined. Here, we show that compared to individuals with a resolved SARS-CoV-2 infection (and no persistent symptoms), individuals with prolonged PASC-CVS had elevated levels of pro-inflammatory cytokines. However, these cytokines were found to be present in trace amounts, such that they could only be detected with the use of novel nanotechnology. Importantly, these trace-level cytokines had a direct effect on the functionality of primary human cardiomyocytes in vitro. Proteomics analyses demonstrated further differences in PASC-CVS and recovered plasma including increased abundance of complement and coagulation associated proteins.

INSTRUMENT(S): ZenoTOF 7600

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Plasma

DISEASE(S): Cardiovascular System Disease,Long Covid

SUBMITTER: Kyle Macauslane

LAB HEAD: Benjamin L Schulz

PROVIDER: PXD050202 | Pride | 2024-11-01

REPOSITORIES: Pride

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			Action	DRS
	20231206_Schulz_LCOVID_Plasma_002.wiff	Wiff
	20231206_Schulz_LCOVID_Plasma_002.wiff.scan	Wiff
	20231206_Schulz_LCOVID_Plasma_003.wiff	Wiff
	20231206_Schulz_LCOVID_Plasma_003.wiff.scan	Wiff
	20231206_Schulz_LCOVID_Plasma_004.wiff	Wiff

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Project description:In the last two years, the coronavirus disease 19 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a scientific and social challenge worldwide. Vaccines have been the most effective intervention for reducing virus transmission and disease severity. However, virus genetic variants are still circulating among vaccinated individuals with different symptomatology disease cases. Understanding the protective or disease associated mechanisms in vaccinated individuals is relevant to advance in vaccine development and implementation. To address this objective, serum protein profiles were characterized by quantitative proteomics and data analysis algorithms in four cohorts of vaccinated individuals uninfected and SARS-CoV-2 infected with asymptomatic, nonsevere and severe disease symptomatology. The results showed that immunoglobulins were the most overrepresented proteins in infected cohorts when compared to PCR-negative individuals. The immunoglobulin profile varied between different infected cohorts and correlated with protective or disease associated capacity. Overrepresented immunoglobulins in PCR-positive individuals correlated with protective response against SARS-CoV-2, other viruses, and thrombosis in asymptomatic cases. In nonsevere cases, correlates of protection against SARS-CoV-2 and HBV together with risk of myasthenia gravis and allergy and autoantibodies were observed. Patients with severe symptoms presented risk for allergy, chronic idiopathic thrombocytopenic purpura, and autoantibodies. The analysis of underrepresented immunoglobulins in PCR-positive compared to PCR-negative individuals identified vaccine-induced protective epitopes in various coronavirus proteins including the Spike receptor-binding domain RBD. Non-immunoglobulin proteins were associated with COVID-19 symptoms and biological processes. These results evidence host-associated differences in response to vaccination and the possibility of improving vaccine efficacy against SARS-CoV-2.

Dataset Information

Cardiovascular symptoms of PASC are associated with trace-level circulatory cytokines that affect the function of primary human cardiomyocytes

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