Covid-19 triggers metabolic signatures in children that mirror cardiac risk in adults

Covid-19 triggers metabolic signatures in children that mirror cardiac risk in adults

A new proteomics study shows that even short-term Covid-19 in children can outpace blood markers of cardiovascular risk, particularly in patients with MIS-C, challenging the notion that children recover unscathed.

Observational reports have led many clinicians to believe that children generally experience milder outcomes in SARS-CoV-2 infections, in contrast to their adult counterparts. However, the underlying metabolic effects have not been fully characterized. In a recent studyJournal of Proteome ResearchA collaborative research team from Australia's National Phenome Center and Harvard analyzed blood plasma samples (n=147) from pediatric patients to investigate these effects.

Advanced blood characterization tools identified acute disturbances in lipid and lipoprotein metabolism, known markers of long-term cardiovascular risk. During acute Covid-19 infections, children have plasma temperatures similar to those in adults with severe Covid-19, which contain markers associated with long-term cardiovascular risk. This study challenges assumptions of universally mild pediatric Covid-19 and calls for further investigation and surveillance in children to mitigate future cardiovascular disease (CVD) risks.

background

Children have long been seen as largely unaffected by the long-term consequences of Covid-19, particularly when it comes to heart health. The emergence of multisystem inflammatory syndrome in children (MIS-C) as well as broader reports of persistent symptoms in pediatric long Covid cases has increased these perceptions, which has shown that SARS-CoV-2 can trigger life-threatening systemic inflammatory diseases from mild CoVID-associated respiratory illnesses.

MIS-C is a rare but serious disease characterized by potentially life-threatening multi-organ inflammation across cardiovascular, gastrointestinal, and mucocutaneous systems. A growing body of evidence suggests shared metabolic pathways between some post-covid diseases and the severe inflammatory response in MIS-C.

Unfortunately, given the relative newness of Covid-19 and the prevailing scientific views on child outcomes on associated SARS-CoV-2 outcomes, only a handful of studies have examined the ongoing metabolic effects of pediatric COVID-19. Data from blood-based biomarker analyses, particularly those that identify previously undetected, long-term cardiovascular risks, are lacking.

About the study

The present study aims to address existing scientific knowledge gaps by conducting a comprehensive set of advanced biochemical and proteomic assays on children during acute Covid-19 and MIS-C.

Study data were obtained from the Pediatric COVID-19 Biorepository at Massachusetts General Hospital in the USA and included sociodemographic information and medical health records. Biometric measures and plasma samples were collected from each participant once during their acute illness.

The Centers for Disease Control and Prevention (CDC) definitions were used to classify study participants into three categories: 1. healthy children who have never been infected by SARS-CoV-2 (healthy), 2. acute Covid-19 (Covid-19), and 3. confirmed MIS-C cases (MIS-C). All participant plasma samples were subjected to high-resolution liquid chromatography-tandem mass spectrometry (LC-MS/MS) to facilitate the identification of a broad spectrum of metabolites.

To obtain a detailed metabolic fingerprint, researchers used nuclear magnetic resonance (NMR) data to identify and quantify cholesterol and its derivatives, triglycerides and inflammatory markers. They then compared these metabolic profiles with those of a previously studied cohort of adults with Covid-19.

Statistical analyzes included principal component analyzes (PCAs) to identify primary data variations, forest data imputation (for missing data), and orthogonal projection latent structure discriminant analysis (OPLS-DA) to explain data variance in infection. Data were then analyzed and visualized using multivariate analyzes adjusting for demographics and other confounding factors.

Study results

The final sample cohort included 147 children. CDC guidelines classified these participants into three groups: 1, 66 healthy children (no SARS-CoV-2 infections), 2, 55 with acute Covid-199 infections (25% severe), and 3, 26 with MIS-C. MIS-C patients presented symptoms involving cardiovascular, mucocutaneous, and gastrointestinal systems.

The study results showed several alarming results:

Children with Covid-19 (particularly with MIS-C) showed significant changes in lipid metabolism during their acute illness. These include elevated triglyceride levels indicative of pediatric hypertriglyceridemia, a marked reduction in high-density lipoprotein (HDL) concentrations and increased inflammatory lipoproteins, and certain low-density lipoprotein (LDL) particles.

Elevated triglycerides and specific LDL particles are hallmarks of early cardiovascular disease, while HDL cholesterol is a known protective factor against cardiovascular disease (CVD). These results therefore suggest that children with acute Covid-19 (particularly MIS-C patients) have a profile that may put them at increased risk of chronic CVD outcomes.

Lipoprotein analyzes showed that the inflammatory lipoproteins in children with Covid-19 and MIS-C showed strong similarity to those in adults with severe Covid-19.

The authors also noted a high prevalence of overweight and obesity in the patient cohorts, suggesting that they may contribute a factor exacerbating the observed lipid abnormalities and future cardiovascular risks.

Notably, individuals in the healthy control group did not reflect any of these results, indicating a Covid-19-specific metabolic shift in childhood patients.

Conclusions

The present study debunks the reassuring assumption that children experience mild Covid-19 infections without lasting consequences. It highlights that children with acute Covid-19 and MIS-C develop metabolic profiles that closely resemble those containing markers of future cardiovascular risks. In particular, MIS-C patients demonstrated significant metabolic dysfunction and potential long-term cardiovascular risk.

These findings highlight the need for further investigation into the lasting effects of SARS-CoV-2 infection on pediatric health. Clinicians and public health officials must now consider that follow-up beyond respiratory recovery may be warranted to facilitate timely treatment and reduce potential long-term health effects.

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