Tweet
J Med Virol
. 2026 Apr;98(4):e70932.
doi: 10.1002/jmv.70932.
Multiorgan Molecular Landscape of Severe COVID-19 Revealed by Consensus Gene Signatures and RAB8B Targeting
Jonathan Peña Avila 1 2 , Peter Park 1 , Youvika Singh 1 3 , Paulo P Amaral 4 , Ícaro Castro 5 , Felipe Ten-Caten 6 , Viviane Schuch 1 , André N A Gonçalves 1 , Jeevan Giddaluru 1 , Mauro César Cafundó Morais 1 2 , Rodrigo L T Ogava 1 , Thiago Lubiana 1 , Gabriel Amoroso de Castro 7 , Rodrigo Aquino 1 , Luiz Durão 1 , Júlia Raspante Martins 8 , Leandro Jimenez 1 , André G Costa-Martins 1 9 , Patrícia Gonzalez-Dias 1 , Thiago Dominguez Crespo Hirata 1 , Thomaz Lüscher Dias 1 , Débora Guerra Peixe 5 , Adriana Simizo 10 , Juan Carlo Santos E Silva 1 2 , Amanda Pereira Vasconcelos 1 , Marcelo Berçot Rodrigues 11 12 , Bianca G Castelucci 11 , João Victor Virgillio-da-Silva 11 , Larissa Menezes 11 , Pedro M Moraes-Vieira 11 , Otavio Cabral-Marques 1 5 13 14 15 , Helder I Nakaya 1 2 10
Affiliations
Severe COVID-19 involves hyperinflammation and multiorgan pathology, but consistent gene signatures remain elusive. We aimed to identify consensus transcriptomic signatures and molecular mechanisms in severe COVID-19. We performed an integrative analysis of 39 studies spanning 11 tissue types, 1551 bulk RNA-seq samples, and over 2 million single cells. A vote-counting strategy combined with a systems-biology approach was applied to detect consensus differentially expressed genes (DEGs). Pathways related to interferon/TNF-α signaling, hypoxia response, and platelet activation were consistently enriched across data sets. Among consensus DEGs-such as IFITM3, BCL2A1, CAMK2D, and CCR1-RAB8B was prioritized for functional validation based on its recurrence in ~45% of tissues and its known role in vesicle trafficking, a process intimately linked to viral life cycles. Molecular dynamics simulations and in vitro assays in SARS-CoV-2-infected CaCo-2 cells demonstrated that RAB8B modulates VAMP-3 clustering and intracellular trafficking. Silencing of Rab8b-1 and Rab8b-2 reduced viral infection by 30% (p = 0.0302) and 76% (p < 0.001), respectively. This study defines robust consensus signatures and positions RAB8B as a critical host factor and potential therapeutic target in severe COVID-19. Further exploration of RAB8B inhibitors is warranted to explore therapeutic utility. An interactive database at https://covidatlas.sysbio.tools/.
Keywords: RAB8B; SARS‐CoV‐2; bulk RNA‐seq; gene expression; scRNA‐seq; severe COVID‐19.
. 2026 Apr;98(4):e70932.
doi: 10.1002/jmv.70932.
Multiorgan Molecular Landscape of Severe COVID-19 Revealed by Consensus Gene Signatures and RAB8B Targeting
Jonathan Peña Avila 1 2 , Peter Park 1 , Youvika Singh 1 3 , Paulo P Amaral 4 , Ícaro Castro 5 , Felipe Ten-Caten 6 , Viviane Schuch 1 , André N A Gonçalves 1 , Jeevan Giddaluru 1 , Mauro César Cafundó Morais 1 2 , Rodrigo L T Ogava 1 , Thiago Lubiana 1 , Gabriel Amoroso de Castro 7 , Rodrigo Aquino 1 , Luiz Durão 1 , Júlia Raspante Martins 8 , Leandro Jimenez 1 , André G Costa-Martins 1 9 , Patrícia Gonzalez-Dias 1 , Thiago Dominguez Crespo Hirata 1 , Thomaz Lüscher Dias 1 , Débora Guerra Peixe 5 , Adriana Simizo 10 , Juan Carlo Santos E Silva 1 2 , Amanda Pereira Vasconcelos 1 , Marcelo Berçot Rodrigues 11 12 , Bianca G Castelucci 11 , João Victor Virgillio-da-Silva 11 , Larissa Menezes 11 , Pedro M Moraes-Vieira 11 , Otavio Cabral-Marques 1 5 13 14 15 , Helder I Nakaya 1 2 10
Affiliations
- PMID: 42015392
- DOI: 10.1002/jmv.70932
Severe COVID-19 involves hyperinflammation and multiorgan pathology, but consistent gene signatures remain elusive. We aimed to identify consensus transcriptomic signatures and molecular mechanisms in severe COVID-19. We performed an integrative analysis of 39 studies spanning 11 tissue types, 1551 bulk RNA-seq samples, and over 2 million single cells. A vote-counting strategy combined with a systems-biology approach was applied to detect consensus differentially expressed genes (DEGs). Pathways related to interferon/TNF-α signaling, hypoxia response, and platelet activation were consistently enriched across data sets. Among consensus DEGs-such as IFITM3, BCL2A1, CAMK2D, and CCR1-RAB8B was prioritized for functional validation based on its recurrence in ~45% of tissues and its known role in vesicle trafficking, a process intimately linked to viral life cycles. Molecular dynamics simulations and in vitro assays in SARS-CoV-2-infected CaCo-2 cells demonstrated that RAB8B modulates VAMP-3 clustering and intracellular trafficking. Silencing of Rab8b-1 and Rab8b-2 reduced viral infection by 30% (p = 0.0302) and 76% (p < 0.001), respectively. This study defines robust consensus signatures and positions RAB8B as a critical host factor and potential therapeutic target in severe COVID-19. Further exploration of RAB8B inhibitors is warranted to explore therapeutic utility. An interactive database at https://covidatlas.sysbio.tools/.
Keywords: RAB8B; SARS‐CoV‐2; bulk RNA‐seq; gene expression; scRNA‐seq; severe COVID‐19.