Multi-Omic Approaches to Solve Post-Acute COVID-19 (MOSAIC)

Study Aim

The purpose of this study is to facilitate early detection of ME/CFS in people with Long COVID and better understand disease progression.

Investigators

  • Alain Moreau, PhD
  • Jonas Bergquist, MD, PhD
  • Christopher Armstrong, PhD

Updates and Potential

  • We identified a differential methylation signature that can distinguish between Long COVID patients who will remain severely affected and those likely to recover over time.
  • Several affected genes represent potential therapeutic targets for accelerating Long COVID recovery.
  • Two manuscripts on DNA methylation are in progress.
  • Two manuscripts related to the role of circulating microRNAs in Long COVID pathogenesis are in progress.

An intriguing finding from the Long COVID cohort (non-hospitalized patients) is that around 24% of them had scoliosis during adolescence, which is a significantly higher rate than the 2-4% seen in the general population. Our proteomic data revealed significant upregulation of BNC2 in certain plasma samples—a marker linked to scoliosis onset and progression. It’s unclear whether preexisting elevated BNC2 levels predispose individuals to Long COVID or if Long COVID may reactivate scoliosis through BNC2 stimulation.

STUDY HYPOTHESIS AND DESCRIPTION

Despite the myriad of symptoms that patients can have with “Long COVID”, it appears that there are common pathogenic mechanisms for those disparate symptoms. While ME/CFS researchers understand that viral insult combined with other factors likely contribute to the onset of ME/CFS and related conditions like FM, it is important to identify the molecular mechanisms leading to these conditions as well as how to discriminate ME/CFS from other types of long-term sequelae (e.g., neurological conditions, respiratory dysfunction) as early as possible among COVID-19 long-haulers. 

Such an approach can lead to the development of algorithms predicting their clinical trajectories. It also offers an opportunity to help COVID-19 long-haulers as well as ME/CFS patients to better understand the progression of the condition and provide insights to identify targeted treatment strategies through precision medicine. Finally, as ME/CFS has historically followed viral outbreaks, the study of COVID-19 long-haulers may shed light on post-infectious fatigue syndrome following infections other than COVID-19.

OBJECTIVES

Test tube with blood in the hand.

  1. Identify the global expression profiling of circulating microRNAs among different Long COVID subsets.
  2. Analyze the global DNA methylation profiling of different Long COVID subsets.
  3. Analyze the global proteomic plasma profiling of different Long COVID subsets.
  4. Analyze the global metabolomic plasma and urine profiling of Long COVID subsets.