Title Participants Abstract "Immunovirological and environmental screening reveals actionable risk factors for fatal COVID-19 during post-vaccination nursing home outbreaks" "Lize Cuypers, Els Keyaerts, Samuel L Hong, Sarah Gorissen, Soraya Maria Menezes, Marick Starick, Jan Van Elslande, Matthias Weemaes, Tony Wawina-Bokalanga, Joan Marti-Carreras, Bert Vanmechelen, Bram Van Holm, Mandy Bloemen, Jean-Michel Dogne, François Dufrasne, Keith Durkin, Jean Ruelle, Ricardo De Mendonca, Elke Wollants, Pieter Vermeersch, Ruddy Wattiez, Michael Peeters, Kate Bakelants, Sarah Denayer, Cécile Meex, Laurent Gillet, Maria Artesi, Marie-Pierre Hayette, Sébastien Bontems, Vincent Bours, Claire Gourzonès, Olivier Ek, Fabrice Bureau, Benoit Kabamba, Jean-Luc Gala, Bertrand Bearzatto, Jérôme Ambroise, Arnaud Marchant, Coralie Henin, Benoit Haerlingen, Marie-Luce Delforge, Carl Vael, Lynsey Berckmans, Philippe Selhorst, Kevin Ariën, Sonia Van Dooren, Bruno Hinckel, Hideo Imamura, Toon Janssen, Ben Caljon, Oriane Soetens, Denis Piérard, Thomas Demuyser, Charlotte Michel, Olivier Vandenberg, Sigi van den Wijngaert, Giulia Zorzi, Philippe Van Lint, Walter Verstrepen, Reinout Naesens, Sarah Van Lent, Pascale Hilbert, Sylvain Brohée, Pierre-Emmanuel Léonard, Deniz Karadurmus, Jeremie Gras, Damien Féret, Barbara Lambert, Anne Vankeerberghen, Astrid Holderbeke, Hans De Beenhouwer, Lien Cattoir, Christine Lammens, Basil Britto Xavier, Marie Le Mercier, Jasmine Coppens, Veerle Matheeussen, Herman Goossens, Geert A. Martens, Koen Swaerts, Frederik Van Hoecke, Dieter Desmet, Patrick Descheemaeker, Pierre Bogaerts, Jonathan Degosserie, Olivier Denis, Te-Din Huang, Dagmar Obbels, Hanne Valgaeren, Johan Frans, Annick Smismans, Paul-Emile Claus, Denise Veltman, Truus Goegebuer, Ann Lemmens, Bea Van den Poel, Sonja De Bock, Wim Laffut, Ellen Van Even, Jos Van Acker, Charlotte Verfaillie, Elke Vanlaere, Klara De Rauw, Luc Waumans, Britt Van Meensel, Reinoud Cartuyvels, Marijke Raymaekers, Bruno Verhasselt, Jorn Hellemans, Merijn Vanhee, Marijke Reynders, Caroline Boulouffe, Achille Djiena, Caroline Broucke, Boudewijn Catry, Katrien Lagrou, Marc Van Ranst, Johan Neyts, Guy Baele, Piet Maes, Emmanuel André, Simon Dellicour, J Van Weyenbergh" "Coronavirus Disease 2019 (COVID-19) vaccination has resulted in excellent protection against fatal disease, including in older adults. However, risk factors for post-vaccination fatal COVID-19 are largely unknown. We comprehensively studied three large nursing home outbreaks (20–35% fatal cases among residents) by combining severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) aerosol monitoring, whole-genome phylogenetic analysis and immunovirological profiling of nasal mucosa by digital nCounter transcriptomics. Phylogenetic investigations indicated that each outbreak stemmed from a single introduction event, although with different variants (Delta, Gamma and Mu). SARS-CoV-2 was detected in aerosol samples up to 52 d 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 transcriptomic and genomic signatures uncovered a unique IRF3 low/ IRF7 high 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." "Comprehensive Antiretroviral Restriction Factor Profiling Reveals the Evolutionary Imprint of the exVivo and in Vivo IFN-β Response in HTLV-1-Associated Neuroinflammation" "Soraya Menezes, Tim Dierckx, Jurgen Vercauteren, Johan Van Weyenbergh" "HTLV-1-Associated Myelopathy (HAM/TSP) is a progressive neuroinflammatory disorder for which no disease-modifying treatment exists. Modest clinical benefit from type I interferons (IFN-α/β) in HAM/TSP contrasts with its recently identified IFN-inducible gene signature. In addition, IFN-α treatment in vivo decreases proviral load and immune activation in HAM/TSP, whereas IFN-β therapy decreases tax mRNA and lymphoproliferation. We hypothesize this ""IFN paradox"" in HAM/TSP might be explained by both cell type- and gene-specific effects of type I IFN in HTLV-1-associated pathogenesis. Therefore, we analyzed ex vivo transcriptomes of CD4+ T cells, PBMCs and whole blood in healthy controls, HTLV-1-infected individuals, and HAM/TSP patients. First, we used a targeted approach, simultaneously quantifying HTLV-1 mRNA (HBZ, Tax), proviral load and 42 host genes with known antiretroviral (anti-HIV) activity in purified CD4+ T cells. This revealed two major clusters (""antiviral/protective"" vs. ""proviral/deleterious""), as evidenced by significant negative (TRIM5/TRIM22/BST2) vs. positive correlation (ISG15/PAF1/CDKN1A) with HTLV-1 viral markers and clinical status. Surprisingly, we found a significant inversion of antiretroviral activity of host restriction factors, as evidenced by opposite correlation to in vivo HIV-1 vs. HTLV-1 RNA levels. The anti-HTLV-1 effect of antiviral cluster genes was significantly correlated to their adaptive chimp/human evolution score, for both Tax mRNA and PVL. Six genes of the proposed antiviral cluster underwent lentivirus-driven purifying selection during primate evolution (TRIM5/TRIM22/BST2/APOBEC3F-G-H), underscoring the cross-retroviral evolutionary imprint. Secondly, we examined the genome-wide type I IFN response in HAM/TSP patients, following short-term ex vivo culture of PBMCs with either IFN-α or IFN-β. Microarray analysis evidenced 12 antiretroviral genes (including TRIM5α/TRIM22/BST2) were significantly up-regulated by IFN-β, but not IFN-α, in HAM/TSP. This was paralleled by a significant decrease in lymphoproliferation by IFN-β, but not IFN-α treatment. Finally, using published ex vivo whole blood transcriptomic data of independent cohorts, we validated the significant positive correlation between TRIM5, TRIM22, and BST2 in HTLV-1-infected individuals and HAM/TSP patients, which was independent of the HAM/TSP disease signature. In conclusion, our results provide ex vivo mechanistic evidence for the observed immunovirological effect of in vivo IFN-β treatment in HAM/TSP, reconcile an apparent IFN paradox in HTLV-1 research and identify biomarkers/targets for a precision medicine approach." "Longitudinal patterns of inflammatory mediators after acute HIV infection correlate to intact and total reservoir" "Jozefien De Clercq, Marie-Angélique De Scheerder, Virginie Mortier, Chris Verhofstede, Stefaan J Vandecasteele, Sabine Allard, Coca Necsoi, Stéphane De Wit, Sarah Gerlo, Linos Vandekerckhove" "BACKGROUND: Despite the beneficial effects of antiretroviral therapy (ART) initiation during acute HIV infection (AHI), residual immune activation remains a hallmark of treated HIV infection.METHODS: Plasma concentrations of 40 mediators were measured longitudinally in 39 early treated participants of a Belgian AHI cohort (HIV+) and in 21 HIV-negative controls (HIV-). We investigated the association of the inflammatory profile with clinical presentation, plasma viral load, immunological parameters, and in-depth characterization of the HIV reservoir.RESULTS: While levels of most soluble mediators normalized with suppressive ART, we demonstrated the persistence of a pro-inflammatory signature in early treated HIV+ participants in comparison to HIV- controls. Examination of these mediators demonstrated a correlation with their levels during AHI, which seemed to be viremia-driven, and suggested involvement of an activated myeloid compartment, IFN-γ-signaling, and inflammasome-related pathways. Interestingly, some of these pro-inflammatory mediators correlated with a larger reservoir size and slower reservoir decay. In contrast, we also identified soluble mediators which were associated with favorable effects on immunovirological outcomes and reservoir, both during and after AHI.CONCLUSION: These data highlight how the persistent pro-inflammatory profile observed in early ART treated individuals is shaped during AHI and is intertwined with viral dynamics."