Blood transcriptomics reveal persistent SARS-CoV-2 RNA and candidate biomarkers in Long COVID patients

Abstract:

With an estimated 65 million individuals suffering from Long COVID, validated therapeutic strategies as well as non-invasive biomarkers are direly needed to guide clinical management. We used blood digital transcriptomics in search of viral persistence and Long COVID diagnostic biomarkers in a real-world, general practice-based setting with a long clinical follow-up.

We demonstrate systemic SARS-CoV-2 persistence for more than 2 years after acute COVID-19 infection. A 2-gene biomarker, including SARS-CoV-2 antisense RNA, correctly classifies Long COVID with 93.8% sensitivity and 91.7% specificity. Specific immune transcripts and immunometabolism score correlate to systemic viral load and patient-reported anxiety/depression, providing mechanistic links as well as therapeutic targets to tackle Long COVID.

Source: Soraya Maria MENEZES, MARC JAMOULLE, Maria P Carletto, Bram Van Holm, Leen Moens, Isabelle Meyts, Piet Maes, Johan Van Weyenbergh. Blood transcriptomics reveal persistent SARS-CoV-2 RNA and candidate biomarkers in Long COVID patients. medRxiv 2024.01.14.24301293; doi: https://doi.org/10.1101/2024.01.14.24301293 https://www.medrxiv.org/content/10.1101/2024.01.14.24301293v1 (Full text available as PDF file)

Incidence of persistent SARS-CoV-2 gut infection in patients with a history of COVID-19: Insights from endoscopic examination

Abstract:

Background and study aims Gut infection is common during acute COVID-19, and persistent SARS-CoV-2 gut infection has been reported months after the initial infection, potentially linked to long-COVID syndrome. This study tested the incidence of persistent gut infection in patients with a history of COVID-19 undergoing endoscopic examination.

Patients and methods Endoscopic biopsies were prospectively collected from patients with previous COVID-19 infection undergoing upper or lower gastrointestinal endoscopy (UGE or LGE). Immunohistochemistry was used to detect the presence of persistent SARS-CoV-2 nucleocapsid proteins.

Results A total of 166 UGEs and 83 LGE were analyzed. No significant differences were observed between patients with positive and negative immunostaining regarding the number of previous COVID-19 infections, time since the last infection, symptoms, or vaccination status. The incidence of positive immunostaining was significantly higher in UGE biopsies than in LGE biopsies (37.34% vs. 16.87%, P =0.002). Smokers showed a significantly higher incidence of positive immunostaining in the overall cohort and UGE and LGE subgroups ( P <0.001). Diabetic patients exhibited a significantly higher incidence in the overall cohort ( P =0.002) and UGE subgroup ( P =0.022), with a similar trend observed in the LGE subgroup ( P =0.055).

Conclusions Gut mucosal tissues can act as a long-term reservoir for SARS-CoV-2, retaining viral particles for months following the primary COVID-19 infection. Smokers and individuals with diabetes may be at an increased risk of persistent viral gut infection. These findings provide insights into the dynamics of SARS-CoV-2 infection in the gut and have implications for further research.

Source: Hany M, Sheta E, Talha A, Anwar M, Selima M, Gaballah M, Zidan A, Ibrahim M, Agayby ASS, Abouelnasr AA, Samir M, Torensma B. Incidence of persistent SARS-CoV-2 gut infection in patients with a history of COVID-19: Insights from endoscopic examination. Endosc Int Open. 2024 Jan 5;12(1):E11-E22. doi: 10.1055/a-2180-9872. PMID: 38188925; PMCID: PMC10769582. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10769582/ (Full text)

 

SARS-CoV-2 Spike Protein Accumulation in the Skull-Meninges-Brain Axis: Potential Implications for Long-Term Neurological Complications in post-COVID-19

Abstract:

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), has been associated mainly with a range of neurological symptoms, including brain fog and brain tissue loss, raising concerns about the virus’s acute and potential chronic impact on the central nervous system. In this study, we utilized mouse models and human post-mortem tissues to investigate the presence and distribution of the SARS-CoV-2 spike protein in the skull-meninges-brain axis.

Our results revealed the accumulation of the spike protein in the skull marrow, brain meninges, and brain parenchyma. The injection of the spike protein alone caused cell death in the brain, highlighting a direct effect on brain tissue. Furthermore, we observed the presence of spike protein in the skull of deceased long after their COVID-19 infection, suggesting that the spike’s persistence may contribute to long-term neurological symptoms. The spike protein was associated with neutrophil-related pathways and dysregulation of the proteins involved in the PI3K-AKT as well as complement and coagulation pathway.

Overall, our findings suggest that SARS-CoV-2 spike protein trafficking from CNS borders into the brain parenchyma and identified differentially regulated pathways may present insights into mechanisms underlying immediate and long-term consequences of SARS-CoV-2 and present diagnostic and therapeutic opportunities.

Source: Zhouyi RongHongcheng MaiSaketh KapoorVictor G. PuellesJan CzogallaJulia SchädlerJessica VeringClaire DelbridgeHanno SteinkeHannah FrenzelKatja SchmidtÖzüm Sehnaz CaliskanJochen Martin WettengelFatma CherifMayar AliZeynep Ilgin KolabasSelin UlukayaIzabela HorvathShan ZhaoNatalie KrahmerSabina TahirovicAli Önder YildirimTobias B. HuberBenjamin OndruschkaIngo BechmannGregor EbertUlrike ProtzerHarsharan Singh BhatiaFarida HellalAli Ertürk. SARS-CoV-2 Spike Protein Accumulation in the Skull-Meninges-Brain Axis: Potential Implications for Long-Term Neurological Complications in post-COVID-19.