Liquid biomarkers of macrophage dysregulation and circulating spike protein illustrate the biological heterogeneity in patients with post-acute sequelae of COVID-19

Abstract

Post-acute sequelae of COVID-19 (PASC) are long-term consequences of SARS-CoV-2 infection that can substantially impair quality of life. Underlying mechanisms ranging from persistent virus to innate and adaptive immune dysregulation have been discussed. Here, we profiled plasma of 181 individuals from the cohort study for digital health research in Germany (DigiHero) including individuals after mild to moderate COVID-19 with or without PASC and uninfected controls. We focused on soluble factors related to monocyte/macrophage biology and on circulating SARS-CoV-2 spike (S1) protein as potential biomarker for persistent viral reservoirs. At a median time of eight months after infection, we found pronounced dysregulation in almost all tested soluble factors including both pro-inflammatory and pro-fibrotic cytokines. These perturbations were remarkably independent of ongoing symptoms, but further correlation and regression analyses suggested PASC specific patterns involving CCL2/MCP-1 and IL-8 as well as long-term persistence of high IL-5 and IL-17F levels. None of the analyzed factors correlated with the detectability or levels of circulating S1 indicating that this represents an independent subset of patients with PASC. This data confirms prior evidence of immune dysregulation and persistence of viral protein in PASC and illustrates its biological heterogeneity that still awaits correlation with clinically defined PASC subtypes.

Long COVID‐19 gastrointestinal related disorders and traditional Chinese medicine: A network target‐based approach

“…Interestingly, these effects could be a key element in the treatment of Long COVID-19, characterized by high levels of IL-17 and low levels of IL-10 (Queiroz et al, 2022). It is noteworthy also 6-gingerol ability to decrease IL-1 and TNF-α expression, as these cytokines are upregulated in Long COVID-19 (Ajayi et al, 2015;Schultheiß et al, 2022). This compound has also demonstrated activity in an experimental model of chronic ulcerative colitis (100 mg/kg), where it reduces inflammation and oxidative stress and restores the balance between Th17/Treg cells (100 and 250 mg/kg for 14 days) (Ajayi et al, 2018;Sheng, Wu, Dai, Ji, et al, 2020).…”

“…These events result from a complex interplay among inflammatory factors, oxidative stress, and microbiome alterations (Merra et al, 2022). From a constant low-grade inflammation status up to a hyperinflammation status is observed in Long COVID-19 patients, and it is associated with an increase of pro-inflammatory cytokines in serum, such as IL-2, IL-17, IL-1β, IL-6, TNF-α, and a decrease of several anti-inflammatory cytokines such as IL-4 and IL-10 (Queiroz et al, 2022;Schultheiß et al, 2022). Long COVID-19 is also related to increased oxidative stress and gut microbiota alterations (Vollbracht & Kraft, 2022).…”

Baseline Characteristics in the Remote Diet Intervention to REduce long-COVID Symptoms Trial (ReDIRECT)

“…Online LC communities evolved early in the pandemic, with patients sharing experiences of the after-effects of COVID-19 on social media and collectively coining the term "Long Covid" (Callard & Perego, 2021). At a time of social distancing and with evidence about LC first emerging through these patient groups, online communities were an important source of support for LC patients, providing a safe space to speak about symptoms and concerns, filling a gap in care, and helping patients find validation in others sharing similar experiences (Day, 2022;Russell et al, 2022).…”