Vaccination after developing long COVID: Impact on clinical presentation, viral persistence, and immune responses.

BACKGROUND: Vaccination protects against severe COVID-19 manifestations. For those with post-COVID-19 conditions (PCC) or long COVID, the impact of COVID-19 vaccination on the evolution of symptoms, immune responses, and viral persistence is unclear. METHODS: In this prospective observational cohort study, we evaluated the number of PCC symptoms, affected organ systems, and psychological well-being scores before and after patients with PCC received COVID-19 vaccination. We simultaneously evaluated biomarkers of systemic inflammation and levels of plasma cytokines/chemokines. We measured plasma and intracellular levels of SARS-CoV-2 antigens, and immunoreactivity to SARS-CoV-2 antigens in blood. RESULTS: COVID-19 vaccination was associated with decreases in number of PCC symptoms (pre-vaccination: 6.56 ± 3.1 vs post-vaccination: 3.92 ± 4.02; P <0.001) and affected organ systems (pre-vaccination: 3.19 ± 1.04 vs post-vaccination: 1.89 ± 1.12; P <0.001), and increases in World Health Organization (WHO)-5 Well-Being Index Scores (pre-vaccination: 42.67 ± 22.76 vs post-vaccination: 56.15 ± 22.83; P <0.001). Patients with PCC also had significantly decreased levels of several pro-inflammatory plasma cytokines/chemokines after COVID-19 vaccination including sCD40L, GRO-⍺, macrophage inflammatory protein (MIP)-1⍺, interleukin (IL)-12p40, G-colony stimulating factor (CSF), M-CSF, IL-1ß, and stem cell factor (SCF). PCC participants presented a certain level of immunoreactivity toward SARS-CoV-2, that was boosted with vaccination. SARS-CoV-2 S1 antigen persisted in the blood of PCC participants, mostly in non-classical monocytes, regardless of participants receiving vaccination. CONCLUSIONS: Our study shows higher pro-inflammatory responses associated with PCC symptoms and brings forward a possible role for vaccination in mitigating PCC symptoms by decreasing systemic inflammation. We also observed persistence of viral products independent of vaccination that could be involved in perpetuating inflammation through non-classical monocytes.

DNA Methylomes Reveal Biological Networks Involved in Human Eye Development, Functions and Associated Disorders.

This work provides a comprehensive CpG methylation landscape of the different layers of the human eye that unveils the gene networks associated with their biological functions and how these are disrupted in common visual disorders. Herein, we firstly determined the role of CpG methylation in the regulation of ocular tissue-specification and described hypermethylation of retinal transcription factors (i.e., PAX6, RAX, SIX6) in a tissue-dependent manner. Second, we have characterized the DNA methylome of visual disorders linked to internal and external environmental factors. Main conclusions allow certifying that crucial pathways related to Wnt-MAPK signaling pathways or neuroinflammation are epigenetically controlled in the fibrotic disorders involved in retinal detachment, but results also reinforced the contribution of neurovascularization (ETS1, HES5, PRDM16) in diabetic retinopathy. Finally, we had studied the methylome in the most frequent intraocular tumors in adults and children (uveal melanoma and retinoblastoma, respectively). We observed that hypermethylation of tumor suppressor genes is a frequent event in ocular tumors, but also unmethylation is associated with tumorogenesis. Interestingly, unmethylation of the proto-oncogen RAB31 was a predictor of metastasis risk in uveal melanoma. Loss of methylation of the oncogenic mir-17-92 cluster was detected in primary tissues but also in blood from patients.