tetano
Editor, Senior Moderator
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[SUP] 1 2 [/SUP], Peter Park[SUP] 1 [/SUP], Youvika Singh[SUP] 1 3 [/SUP], Paulo P Amaral[SUP] 4 [/SUP], Ícaro Castro[SUP] 5 [/SUP], Felipe Ten-Caten[SUP] 6 [/SUP], Viviane Schuch[SUP] 1 [/SUP], André N A Gonçalves[SUP] 1 [/SUP], Jeevan Giddaluru[SUP] 1 [/SUP], Mauro César Cafundó Morais[SUP] 1 2 [/SUP], Rodrigo L T Ogava[SUP] 1 [/SUP], Thiago Lubiana[SUP] 1 [/SUP], Gabriel Amoroso de Castro[SUP] 7 [/SUP], Rodrigo Aquino[SUP] 1 [/SUP], Luiz Durão[SUP] 1 [/SUP], Júlia Raspante Martins[SUP] 8 [/SUP], Leandro Jimenez[SUP] 1 [/SUP], André G Costa-Martins[SUP] 1 9 [/SUP], Patrícia Gonzalez-Dias[SUP] 1 [/SUP], Thiago Dominguez Crespo Hirata[SUP] 1 [/SUP], Thomaz Lüscher Dias[SUP] 1 [/SUP], Débora Guerra Peixe[SUP] 5 [/SUP], Adriana Simizo[SUP] 10 [/SUP], Juan Carlo Santos E Silva[SUP] 1 2 [/SUP], Amanda Pereira Vasconcelos[SUP] 1 [/SUP], Marcelo Berçot Rodrigues[SUP] 11 12 [/SUP], Bianca G Castelucci[SUP] 11 [/SUP], João Victor Virgillio-da-Silva[SUP] 11 [/SUP], Larissa Menezes[SUP] 11 [/SUP], Pedro M Moraes-Vieira[SUP] 11 [/SUP], Otavio Cabral-Marques[SUP] 1 5 13 14 15 [/SUP], Helder I Nakaya[SUP] 1 2 10 [/SUP]
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[SUP] 1 2 [/SUP], Peter Park[SUP] 1 [/SUP], Youvika Singh[SUP] 1 3 [/SUP], Paulo P Amaral[SUP] 4 [/SUP], Ícaro Castro[SUP] 5 [/SUP], Felipe Ten-Caten[SUP] 6 [/SUP], Viviane Schuch[SUP] 1 [/SUP], André N A Gonçalves[SUP] 1 [/SUP], Jeevan Giddaluru[SUP] 1 [/SUP], Mauro César Cafundó Morais[SUP] 1 2 [/SUP], Rodrigo L T Ogava[SUP] 1 [/SUP], Thiago Lubiana[SUP] 1 [/SUP], Gabriel Amoroso de Castro[SUP] 7 [/SUP], Rodrigo Aquino[SUP] 1 [/SUP], Luiz Durão[SUP] 1 [/SUP], Júlia Raspante Martins[SUP] 8 [/SUP], Leandro Jimenez[SUP] 1 [/SUP], André G Costa-Martins[SUP] 1 9 [/SUP], Patrícia Gonzalez-Dias[SUP] 1 [/SUP], Thiago Dominguez Crespo Hirata[SUP] 1 [/SUP], Thomaz Lüscher Dias[SUP] 1 [/SUP], Débora Guerra Peixe[SUP] 5 [/SUP], Adriana Simizo[SUP] 10 [/SUP], Juan Carlo Santos E Silva[SUP] 1 2 [/SUP], Amanda Pereira Vasconcelos[SUP] 1 [/SUP], Marcelo Berçot Rodrigues[SUP] 11 12 [/SUP], Bianca G Castelucci[SUP] 11 [/SUP], João Victor Virgillio-da-Silva[SUP] 11 [/SUP], Larissa Menezes[SUP] 11 [/SUP], Pedro M Moraes-Vieira[SUP] 11 [/SUP], Otavio Cabral-Marques[SUP] 1 5 13 14 15 [/SUP], Helder I Nakaya[SUP] 1 2 10 [/SUP]
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.