Dr. Antonio Condino-Neto

@article{pmid38175961,

title = {Higher COVID-19 pneumonia risk associated with anti-IFN-α than with anti-IFN-ω auto-Abs in children},

author = {Paul Bastard and Adrian Gervais and Maki Taniguchi and Liisa Saare and Karita Särekannu and Tom Le Voyer and Quentin Philippot and Jérémie Rosain and Lucy Bizien and Takaki Asano and Marina Garcia-Prat and Alba Parra-Martínez and Mélanie Migaud and Miyuki Tsumura and Francesca Conti and Alexandre Belot and Jacques G Rivière and Tomohiro Morio and Junko Tanaka and Etienne Javouhey and Filomeen Haerynck and Sotirija Duvlis and Tayfun Ozcelik and Sevgi Keles and Yacine Tandjaoui-Lambiotte and Simon Escoda and Maya Husain and Qiang Pan-Hammarström and Lennart Hammarström and Gloria Ahlijah and Anthony Abi Haidar and Camille Soudee and Vincent Arseguel and Hassan Abolhassani and Sabina Sahanic and Ivan Tancevski and Yoko Nukui and Seiichi Hayakawa and George P Chrousos and Athanasios Michos and Elizabeth-Barbara Tatsi and Filippos Filippatos and Agusti Rodriguez-Palmero and Jesus Troya and Imran Tipu and Isabelle Meyts and Lucie Roussel and Sisse Rye Ostrowski and Laire Schidlowski and Carolina Prando and Antonio Condino-Neto and Nathalie Cheikh and Ahmed A Bousfiha and Jalila El Bakkouri and and and and Pärt Peterson and Aurora Pujol and Romain Lévy and Pierre Quartier and Donald C Vinh and Bertrand Boisson and Vivien Béziat and Shen-Ying Zhang and Alessandro Borghesi and Andrea Pession and Evangelos Andreakos and Nico Marr and Alexios-Fotios A Mentis and Trine H Mogensen and Carlos Rodríguez-Gallego and Pere Soler-Palacin and Roger Colobran and Vallo Tillmann and Bénédicte Neven and Sophie Trouillet-Assant and Petter Brodin and Laurent Abel and Emmanuelle Jouanguy and Qian Zhang and Federico Martinón-Torres and Antonio Salas and Alberto Gómez-Carballa and Luis I Gonzalez-Granado and Kai Kisand and Satoshi Okada and Anne Puel and Aurélie Cobat and Jean-Laurent Casanova},

doi = {10.1084/jem.20231353},

issn = {1540-9538},

year  = {2024},

date = {2024-02-01},

urldate = {2024-02-01},

journal = {J Exp Med},

volume = {221},

number = {2},

abstract = {We found that 19 (10.4%) of 183 unvaccinated children hospitalized for COVID-19 pneumonia had autoantibodies (auto-Abs) neutralizing type I IFNs (IFN-α2 in 10 patients: IFN-α2 only in three, IFN-α2 plus IFN-ω in five, and IFN-α2, IFN-ω plus IFN-β in two; IFN-ω only in nine patients). Seven children (3.8%) had Abs neutralizing at least 10 ng/ml of one IFN, whereas the other 12 (6.6%) had Abs neutralizing only 100 pg/ml. The auto-Abs neutralized both unglycosylated and glycosylated IFNs. We also detected auto-Abs neutralizing 100 pg/ml IFN-α2 in 4 of 2,267 uninfected children (0.2%) and auto-Abs neutralizing IFN-ω in 45 children (2%). The odds ratios (ORs) for life-threatening COVID-19 pneumonia were, therefore, higher for auto-Abs neutralizing IFN-α2 only (OR [95% CI] = 67.6 [5.7-9,196.6]) than for auto-Abs neutralizing IFN-ω only (OR [95% CI] = 2.6 [1.2-5.3]). ORs were also higher for auto-Abs neutralizing high concentrations (OR [95% CI] = 12.9 [4.6-35.9]) than for those neutralizing low concentrations (OR [95% CI] = 5.5 [3.1-9.6]) of IFN-ω and/or IFN-α2.},

keywords = {COVID-19, pneumonia},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37198208,

title = {A novel insight on SARS-CoV-2 S-derived fragments in the control of the host immunity},

author = {Thais Sibioni Berti Bastos and André Guilherme Portela de Paula and Rebeca Bosso Dos Santos Luz and Anali M B Garnique and Marco A A Belo and Silas Fernandes Eto and Dayanne Carla Fernandes and Fausto Klabund Ferraris and Leticia Gomes de Pontes and Tábata Takahashi França and Leonardo José Gil Barcellos and Flavio P Veras and Pamela Bermejo and Giovanna Guidelli and Carla Maneira and Fellipe da Silveira Bezerra de Mello and Gleidson Teixeira and Gonçalo Amarante Guimarães Pereira and Bianca H Ventura Fernandes and Paulo R S Sanches and Helyson Lucas Bezerra Braz and Roberta Jeane Bezerra Jorge and Guilherme Malafaia and Eduardo M Cilli and Danilo da Silva Olivier and Marcos Serrou do Amaral and Renata J Medeiros and Antonio Condino-Neto and Luciani R Carvalho and Glaucia M Machado-Santelli and Ives Charlie-Silva and Jorge Galindo-Villegas and Tárcio Teodoro Braga},

doi = {10.1038/s41598-023-29588-8},

issn = {2045-2322},

year  = {2023},

date = {2023-05-01},

urldate = {2023-05-01},

journal = {Sci Rep},

volume = {13},

number = {1},

pages = {8060},

abstract = {Despite all efforts to combat the pandemic of COVID-19, we are still living with high numbers of infected persons, an overburdened health care system, and the lack of an effective and definitive treatment. Understanding the pathophysiology of the disease is crucial for the development of new technologies and therapies for the best clinical management of patients. Since the manipulation of the whole virus requires a structure with an adequate level of biosafety, the development of alternative technologies, such as the synthesis of peptides from viral proteins, is a possible solution to circumvent this problem. In addition, the use and validation of animal models is of extreme importance to screen new drugs and to compress the organism's response to the disease. Peptides derived from recombinant S protein from SARS-CoV-2 were synthesized and validated by in silico, in vitro and in vivo methodologies. Macrophages and neutrophils were challenged with the peptides and the production of inflammatory mediators and activation profile were evaluated. These peptides were also inoculated into the swim bladder of transgenic zebrafish larvae at 6 days post fertilization (dpf) to mimic the inflammatory process triggered by the virus, which was evaluated by confocal microscopy. In addition, toxicity and oxidative stress assays were also developed. In silico and molecular dynamics assays revealed that the peptides bind to the ACE2 receptor stably and interact with receptors and adhesion molecules, such as MHC and TCR, from humans and zebrafish. Macrophages stimulated with one of the peptides showed increased production of NO, TNF-α and CXCL2. Inoculation of the peptides in zebrafish larvae triggered an inflammatory process marked by macrophage recruitment and increased mortality, as well as histopathological changes, similarly to what is observed in individuals with COVID-19. The use of peptides is a valuable alternative for the study of host immune response in the context of COVID-19. The use of zebrafish as an animal model also proved to be appropriate and effective in evaluating the inflammatory process, comparable to humans.},

keywords = {COVID-19},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37020259,

title = {Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19},

author = {Daniela Matuozzo and Estelle Talouarn and Astrid Marchal and Peng Zhang and Jeremy Manry and Yoann Seeleuthner and Yu Zhang and Alexandre Bolze and Matthieu Chaldebas and Baptiste Milisavljevic and Adrian Gervais and Paul Bastard and Takaki Asano and Lucy Bizien and Federica Barzaghi and Hassan Abolhassani and Ahmad Abou Tayoun and Alessandro Aiuti and Ilad Alavi Darazam and Luis M Allende and Rebeca Alonso-Arias and Andrés Augusto Arias and Gokhan Aytekin and Peter Bergman and Simone Bondesan and Yenan T Bryceson and Ingrid G Bustos and Oscar Cabrera-Marante and Sheila Carcel and Paola Carrera and Giorgio Casari and Khalil Chaïbi and Roger Colobran and Antonio Condino-Neto and Laura E Covill and Ottavia M Delmonte and Loubna El Zein and Carlos Flores and Peter K Gregersen and Marta Gut and Filomeen Haerynck and Rabih Halwani and Selda Hancerli and Lennart Hammarström and Nevin Hatipoğlu and Adem Karbuz and Sevgi Keles and Christèle Kyheng and Rafael Leon-Lopez and Jose Luis Franco and Davood Mansouri and Javier Martinez-Picado and Ozge Metin Akcan and Isabelle Migeotte and Pierre-Emmanuel Morange and Guillaume Morelle and Andrea Martin-Nalda and Giuseppe Novelli and Antonio Novelli and Tayfun Ozcelik and Figen Palabiyik and Qiang Pan-Hammarström and Rebeca Pérez de Diego and Laura Planas-Serra and Daniel E Pleguezuelo and Carolina Prando and Aurora Pujol and Luis Felipe Reyes and Jacques G Rivière and Carlos Rodriguez-Gallego and Julian Rojas and Patrizia Rovere-Querini and Agatha Schlüter and Mohammad Shahrooei and Ali Sobh and Pere Soler-Palacin and Yacine Tandjaoui-Lambiotte and Imran Tipu and Cristina Tresoldi and Jesus Troya and Diederik van de Beek and Mayana Zatz and Pawel Zawadzki and Saleh Zaid Al-Muhsen and Mohammed Faraj Alosaimi and Fahad M Alsohime and Hagit Baris-Feldman and Manish J Butte and Stefan N Constantinescu and Megan A Cooper and Clifton L Dalgard and Jacques Fellay and James R Heath and Yu-Lung Lau and Richard P Lifton and Tom Maniatis and Trine H Mogensen and Horst von Bernuth and Alban Lermine and Michel Vidaud and Anne Boland and Jean-François Deleuze and Robert Nussbaum and Amanda Kahn-Kirby and France Mentre and Sarah Tubiana and Guy Gorochov and Florence Tubach and Pierre Hausfater and and and and and and and and and and Isabelle Meyts and Shen-Ying Zhang and Anne Puel and Luigi D Notarangelo and Stephanie Boisson-Dupuis and Helen C Su and Bertrand Boisson and Emmanuelle Jouanguy and Jean-Laurent Casanova and Qian Zhang and Laurent Abel and Aurélie Cobat},

doi = {10.1186/s13073-023-01173-8},

issn = {1756-994X},

year  = {2023},

date = {2023-04-01},

urldate = {2023-04-01},

journal = {Genome Med},

volume = {15},

number = {1},

pages = {22},

abstract = {BACKGROUND: We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases.nnMETHODS: We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.nnRESULTS: No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P = 1.1 × 10) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR = 3.70[95%CI 1.3-8.2], P = 2.1 × 10). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1-2635.4], P = 3.4 × 10), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3-8.4], P = 7.7 × 10). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD] = 43.3 [20.3] years) than the other patients (56.0 [17.3] years; P = 1.68 × 10).nnCONCLUSIONS: Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old.},

keywords = {COVID-19},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37047078,

title = {Photobiomodulation Reduces the Cytokine Storm Syndrome Associated with COVID-19 in the Zebrafish Model},

author = {Ivana F Rosa and Ana P B Peçanha and Tábata R B Carvalho and Leonardo S Alexandre and Vinícius G Ferreira and Lucas B Doretto and Beatriz M Souza and Rafael T Nakajima and Patrick da Silva and Ana P Barbosa and Leticia Gomes-de-Pontes and Camila G Bomfim and Glaucia M Machado-Santelli and Antonio Condino-Neto and Cristiane R Guzzo and Jean P S Peron and Magaiver Andrade-Silva and Niels O S Câmara and Anali M B Garnique and Renata J Medeiros and Fausto K Ferraris and Leonardo J G Barcellos and Jose D Correia-Junior and Jorge Galindo-Villegas and Mônica F R Machado and Angela Castoldi and Susana L Oliveira and Camila C Costa and Marco A A Belo and Giovane Galdino and Germán G Sgro and Natalia F Bueno and Silas F Eto and Flávio P Veras and Bianca H V Fernandes and Paulo R S Sanches and Eduardo M Cilli and Guilherme Malafaia and Rafael H Nóbrega and Aguinaldo S Garcez and Emanuel Carrilho and Ives Charlie-Silva},

doi = {10.3390/ijms24076104},

issn = {1422-0067},

year  = {2023},

date = {2023-03-01},

urldate = {2023-03-01},

journal = {Int J Mol Sci},

volume = {24},

number = {7},

abstract = {Although the exact mechanism of the pathogenesis of coronavirus SARS-CoV-2 (COVID-19) is not fully understood, oxidative stress and the release of pro-inflammatory cytokines have been highlighted as playing a vital role in the pathogenesis of the disease. In this sense, alternative treatments are needed to reduce the level of inflammation caused by COVID-19. Therefore, this study aimed to investigate the potential effect of red photobiomodulation (PBM) as an attractive therapy to downregulate the cytokine storm caused by COVID-19 in a zebrafish model. RT-qPCR analyses and protein-protein interaction prediction among SARS-CoV-2 and  proteins showed that recombinant Spike protein (rSpike) was responsible for generating systemic inflammatory processes with significantly increased levels of pro-inflammatory (, , , and ), oxidative stress () and energy metabolism () mRNA markers, with a pattern similar to those observed in COVID-19 cases in humans. On the other hand, PBM treatment was able to decrease the mRNA levels of these pro-inflammatory and oxidative stress markers compared with rSpike in various tissues, promoting an anti-inflammatory response. Conversely, PBM promotes cellular and tissue repair of injured tissues and significantly increases the survival rate of rSpike-inoculated individuals. Additionally, metabolomics analysis showed that the most-impacted metabolic pathways between PBM and the rSpike treated groups were related to steroid metabolism, immune system, and lipid metabolism. Together, our findings suggest that the inflammatory process is an incisive feature of COVID-19 and red PBM can be used as a novel therapeutic agent for COVID-19 by regulating the inflammatory response. Nevertheless, the need for more clinical trials remains, and there is a significant gap to overcome before clinical trials can commence.},

keywords = {COVID-19},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36324795,

title = {Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19},

author = {Daniela Matuozzo and Estelle Talouarn and Astrid Marchal and Jeremy Manry and Yoann Seeleuthner and Yu Zhang and Alexandre Bolze and Matthieu Chaldebas and Baptiste Milisavljevic and Peng Zhang and Adrian Gervais and Paul Bastard and Takaki Asano and Lucy Bizien and Federica Barzaghi and Hassan Abolhassani and Ahmad Abou Tayoun and Alessandro Aiuti and Ilad Alavi Darazam and Luis M Allende and Rebeca Alonso-Arias and Andrés Augusto Arias and Gokhan Aytekin and Peter Bergman and Simone Bondesan and Yenan T Bryceson and Ingrid G Bustos and Oscar Cabrera-Marante and Sheila Carcel and Paola Carrera and Giorgio Casari and Khalil Chaïbi and Roger Colobran and Antonio Condino-Neto and Laura E Covill and Loubna El Zein and Carlos Flores and Peter K Gregersen and Marta Gut and Filomeen Haerynck and Rabih Halwani and Selda Hancerli and Lennart Hammarström and Nevin Hatipoğlu and Adem Karbuz and Sevgi Keles and Christèle Kyheng and Rafael Leon-Lopez and Jose Luis Franco and Davood Mansouri and Javier Martinez-Picado and Ozge Metin Akcan and Isabelle Migeotte and Pierre-Emmanuel Morange and Guillaume Morelle and Andrea Martin-Nalda and Giuseppe Novelli and Antonio Novelli and Tayfun Ozcelik and Figen Palabiyik and Qiang Pan-Hammarström and Rebeca Pérez de Diego and Laura Planas-Serra and Daniel E Pleguezuelo and Carolina Prando and Aurora Pujol and Luis Felipe Reyes and Jacques G Rivière and Carlos Rodriguez-Gallego and Julian Rojas and Patrizia Rovere-Querini and Agatha Schlüter and Mohammad Shahrooei and Ali Sobh and Pere Soler-Palacin and Yacine Tandjaoui-Lambiotte and Imran Tipu and Cristina Tresoldi and Jesus Troya and Diederik van de Beek and Mayana Zatz and Pawel Zawadzki and Saleh Zaid Al-Muhsen and Hagit Baris-Feldman and Manish J Butte and Stefan N Constantinescu and Megan A Cooper and Clifton L Dalgard and Jacques Fellay and James R Heath and Yu-Lung Lau and Richard P Lifton and Tom Maniatis and Trine H Mogensen and Horst von Bernuth and Alban Lermine and Michel Vidaud and Anne Boland and Jean-François Deleuze and Robert Nussbaum and Amanda Kahn-Kirby and France Mentre and Sarah Tubiana and Guy Gorochov and Florence Tubach and Pierre Hausfater and and and and and and and and and and Isabelle Meyts and Shen-Ying Zhang and Anne Puel and Luigi D Notarangelo and Stephanie Boisson-Dupuis and Helen C Su and Bertrand Boisson and Emmanuelle Jouanguy and Jean-Laurent Casanova and Qian Zhang and Laurent Abel and Aurélie Cobat},

doi = {10.1101/2022.10.22.22281221},

year  = {2022},

date = {2022-10-01},

urldate = {2022-10-01},

journal = {medRxiv},

abstract = {BACKGROUND: We previously reported inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity in 1-5% of unvaccinated patients with life-threatening COVID-19, and auto-antibodies against type I IFN in another 15-20% of cases.nnMETHODS: We report here a genome-wide rare variant burden association analysis in 3,269 unvaccinated patients with life-threatening COVID-19 (1,301 previously reported and 1,968 new patients), and 1,373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. A quarter of the patients tested had antibodies against type I IFN (234 of 928) and were excluded from the analysis.nnRESULTS: No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was  , with an OR of 27.68 (95%CI:1.5-528.7,  1.1×10  ), in analyses restricted to biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70 [95%CI:1.3-8.2],  2.1×10  ). Adding the recently reported  COVID-19 locus strengthened this enrichment, particularly under a recessive model (OR=19.65 [95%CI:2.1-2635.4];  3.4×10  ). When these 14 loci and  were considered, all individuals hemizygous (  =20) or homozygous (  =5) for pLOF or bLOF variants were patients (OR=39.19 [95%CI:5.2-5037.0],  =4.7×10  ), who also showed an enrichment in heterozygous variants (OR=2.36 [95%CI:1.0-5.9],  =0.02). Finally, the patients with pLOF or bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years;  1.68×10  ).nnCONCLUSIONS: Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old.},

keywords = {COVID-19},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34022333,

title = {A simplified alternative diagnostic algorithm for SARS-CoV-2 suspected symptomatic patients and confirmed close contacts (asymptomatic): A consensus of Latin American experts},

author = {Fabian F Fay and Carlos Arturo Alvarez-Moreno and Pablo E Bonvehi and Carolina Cucho Espinoza and Marco Luis Herrera Hidalgo and Marcel Marcano-Lozada and Carlos M Perez and Alvaro Pulchinelli and Klever Vinicio Sáenz-Flor and Antonio Condino-Neto},

doi = {10.1016/j.ijid.2021.05.011},

issn = {1878-3511},

year  = {2022},

date = {2022-04-01},

urldate = {2022-04-01},

journal = {Int J Infect Dis},

volume = {117},

pages = {130--136},

abstract = {INTRODUCTION: Latin America accounts for one-quarter of global COVID-19 cases and one-third of deaths. Inequalities in the region lead to barriers to the best use of diagnostic tests during the pandemic. There is a need for simplified guidelines that consider the region's limited health resources, international guidelines, medical literature, and local expertise.nnMETHODS: Using a modified Delphi method, 9 experts from Latin American countries developed a simplified algorithm for COVID-19 diagnosis on the basis of their answers to 24 questions related to diagnostic settings, and discussion of the literature and their experiences.nnRESULTS: The algorithm considers 3 timeframes (≤7 days, 8-13 days, and ≥14 days) and presents diagnostic options for each. SARS-CoV-2 real- time reverse transcription-polymerase chain reaction is the test of choice from day 1 to 14 after symptom onset or close contact, although antigen testing may be used in specific circumstances, from day 5 to 7. Antibody assays may be used for confirmation, usually after day 14; however, if clinical suspicion is very high, but other tests are negative, these assays may be used as an adjunct to decision-making from day 8 to 13.nnCONCLUSION: The proposed algorithm aims to support COVID-19 diagnosis decision-making in Latin America.},

keywords = {COVID-19},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35269470,

title = {Severe COVID-19 Shares a Common Neutrophil Activation Signature with Other Acute Inflammatory States},

author = {Lena F Schimke and Alexandre H C Marques and Gabriela Crispim Baiocchi and Caroline Aliane de Souza Prado and Dennyson Leandro M Fonseca and Paula Paccielli Freire and Desirée Rodrigues Plaça and Igor Salerno Filgueiras and Ranieri Coelho Salgado and Gabriel Jansen-Marques and Antonio Edson Rocha Oliveira and Jean Pierre Schatzmann Peron and Gustavo Cabral-Miranda and José Alexandre Marzagão Barbuto and Niels Olsen Saraiva Camara and Vera Lúcia Garcia Calich and Hans D Ochs and Antonio Condino-Neto and Katherine A Overmyer and Joshua J Coon and Joseph Balnis and Ariel Jaitovich and Jonas Schulte-Schrepping and Thomas Ulas and Joachim L Schultze and Helder I Nakaya and Igor Jurisica and Otávio Cabral-Marques},

doi = {10.3390/cells11050847},

issn = {2073-4409},

year  = {2022},

date = {2022-03-01},

urldate = {2022-03-01},

journal = {Cells},

volume = {11},

number = {5},

abstract = {Severe COVID-19 patients present a clinical and laboratory overlap with other hyperinflammatory conditions such as hemophagocytic lymphohistiocytosis (HLH). However, the underlying mechanisms of these conditions remain to be explored. Here, we investigated the transcriptome of 1596 individuals, including patients with COVID-19 in comparison to healthy controls, other acute inflammatory states (HLH, multisystem inflammatory syndrome in children [MIS-C], Kawasaki disease [KD]), and different respiratory infections (seasonal coronavirus, influenza, bacterial pneumonia). We observed that COVID-19 and HLH share immunological pathways (cytokine/chemokine signaling and neutrophil-mediated immune responses), including gene signatures that stratify COVID-19 patients admitted to the intensive care unit (ICU) and COVID-19_nonICU patients. Of note, among the common differentially expressed genes (DEG), there is a cluster of neutrophil-associated genes that reflects a generalized hyperinflammatory state since it is also dysregulated in patients with KD and bacterial pneumonia. These genes are dysregulated at the protein level across several COVID-19 studies and form an interconnected network with differentially expressed plasma proteins that point to neutrophil hyperactivation in COVID-19 patients admitted to the intensive care unit. scRNAseq analysis indicated that these genes are specifically upregulated across different leukocyte populations, including lymphocyte subsets and immature neutrophils. Artificial intelligence modeling confirmed the strong association of these genes with COVID-19 severity. Thus, our work indicates putative therapeutic pathways for intervention.},

keywords = {COVID-19},

pubstate = {published},

tppubtype = {article}

}