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 FYN and 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.
Subject(s)
COVID-19 , Anxiety DisordersABSTRACT
COVID-19 vaccination has resulted in excellent protection against fatal disease, including in the elderly. However, risk factors for post-vaccination fatal COVID-19 are largely unknown. We comprehensively studied three large nursing home outbreaks (20-35% fatal cases) by combining SARS-CoV-2 aerosol monitoring, whole-genome phylogenetic analysis, and immunovirological profiling by digital nCounter transcriptomics. Phylogenetic investigations indicated each outbreak stemmed from a single introduction event, though with different variants (Delta, Gamma, and Mu). SARS-CoV-2 was detected in aerosol samples up to 52 days after the initial infection. Combining demographic, immune and viral parameters, the best predictive models for mortality comprised IFNB1 or age, viral ORF7a and ACE2 receptor transcripts. Comparison with published pre-vaccine fatal COVID-19 signatures and reanalysis of single-cell RNAseq data highlights the unique immune signature in post-vaccine fatal COVID-19 outbreaks. A multi-layered strategy including environmental sampling, immunomonitoring, and early antiviral therapy should be considered to prevent post-vaccination COVID-19 mortality in nursing homes.