Project

PAT-COVID

Host genetics and pathogenetic mechanisms of COVID-19
Application Areas
Research Areas
Research Lines
Staff
WEBSITE

ITB Principal Investigator

Name

Host genetics and pathogenetic mechanisms of COVID-19

Acronym

PAT-COVID

Location

Segrate

Start Date

2021

End Date

2023

Funder

ISTITUTO BUDDISTA ITALIANO SOKA GAKKAI

Partners

Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan (Italy); Università degli Studi di Siena, Siena (Italy); Istituto per lo studio, la prevenzione e la rete oncologica, Florence (Italy); IRCCS Ospedale Policlinico San Martino, Genoa (Italy); Fondazione IRCCS Casa Sollievo della Sofferenza, S. Giovanni Rotondo (FG) (Italy); Fondazione Policlinico Universitario "A. Gemelli" - IRCCS, Rome (Italy) GEN-COVID network (https://sites.google.com/dbm.unisi.it/gen-covid) COVID-19 HGI Human Genetic Iniziative (https://www.covid19hg.org/) Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki, Finland.

Italy was the first European country to experience the SARS-CoV-2 epidemic with unexpected clinical severity. While risk factors such as age and comorbidities are important, they do not fully explain the variability in symptoms, ranging from asymptomatic cases to severe pneumonia. Host genetics is believed to play a key role. This project aims to identify genetic variants associated with COVID-19 severity by collecting biological samples and clinical data from about 3,000 Italian patients. Through integrated genomic analysis and machine learning approaches, the goal is to identify candidate genes for prognosis, personalized treatments, and preventive strategies. In addition, we evaluate the genetic factors affecting the response to the anti-COVID-19 vaccine. Ultimately, the project seeks to accelerate the development of innovative therapies and advanced diagnostic tools to fight the pandemic.

Lammi V, Nakanishi T, Jones SE, Andrews SJ, Karjalainen J, Cortés B, O’Brien HE, Ochoa-Guzman A, Fulton-Howard BE, Broberg M, Haapaniemi HH, Kanai M, Pirinen M, Schmidt A, Mitchell RE, Mousas A, Mangino M, Huerta-Chagoya A, Sinnott-Armstrong N, Cirulli ET, Vaudel M, Kwong ASF, Maiti AK, Marttila MM, Posner DC, Rodriguez AA, Batini C, Minnai F, Dearman AR, Warmerdam CAR, Sequeros CB, Winkler TW, Jordan DM, Rešcenko R, Miano L, Lane JM, Chung RK, Guillen-Guio B, Leavy OC, Carvajal-Silva L, Aguilar-Valdés K, Frangione E, Guare L, Vergasova E, Marouli E, Striano P, Zainulabid UA, Kumar A, Ahmad HF, Edahiro R, Azekawa S; Long COVID Host Genetics Initiative; FinnGen; VA Million Veteran Program; MexGen-COVID Initiative; DBDS Genomic Consortium; GEN-COVID Multicenter Study; PHOSP-COVID Collaborative Group; GENCOV Study; Estonian Biobank Research Team; Luoh SW, Erikstrup C, Pedersen OBV, Lerner-Ellis J, Colombo A, Grzymski JJ, Ishii M, Okada Y, Beckmann ND, Kumari M, Wagner R, Heid IM, John C, Short PJ,
Magnus P, Ansone L, Valenti LVC, Lee SA, Wain LV, Verdugo RA, Banasik K, Geller F, Franke LH, Rakitko A, Duncan EL, Renieri A, Tsilidis KK, de Cid R, Niavarani A, Abner E, Tusié-Luna T, Verma SS, Smith GD, Timpson NJ, Madduri RK, Cho K, Daly MJ, Ganna A, Schulte EC, Richards JB, Ludwig KU, Marks-Hultström M, Zeberg H, Ollila HM. Genome-wide association study of long COVID. Nat Genet. 2025 Jun;57(6):1402-1417. doi: 10.1038/s41588-025-02100-w. Epub 2025 May 21. PMID:40399555; PMCID: PMC12165857.

Esposito M, Minnai F, Copetti M, Miscio G, Perna R, Piepoli A, De Vincentis G, Benvenuto M, D’Addetta P, Croci S, Baldassarri M, Bruttini M, Fallerini C, Brugnoni R, Cavalcante P, Baggi F, Corsini EMG, Ciusani E, Andreetta F, Dragani TA, Fratelli M, Carella M, Mantegazza RE, Renieri A, Colombo F. Human leukocyte antigen variants associate with BNT162b2 mRNA vaccine response. Commun Med (Lond). 2024 Apr 4;4(1):63. doi: 10.1038/s43856-024-00490-2. PMID: 38575714; PMCID: PMC10995155.

Minnai F, Biscarini F, Esposito M, Dragani TA, Bujanda L, Rahmouni S, Alarcón-Riquelme ME, Bernardo D, Carnero-Montoro E, Buti M, Zeberg H, Asselta R, Romero-Gómez M; GEN-COVID Multicenter Study; Fernandez-Cadenas I, Fallerini C, Zguro K, Croci S, Baldassarri M, Bruttini M, Furini S, Renieri A, Colombo F. A genome-wide association study for survival from a multi-centre European study identified variants associated with COVID-19 risk of death. Sci Rep. 2024 Feb 6;14(1):3000. doi: 10.1038/s41598-024-53310-x. PMID: 38321133; PMCID: PMC10847137.

COVID-19 Host Genetics Initiative. A second update on mapping the human genetic architecture of COVID-19. Nature. 2023 Sep;621(7977):E7-E26. doi: 10.1038/s41586-023-06355-3. Epub 2023 Sep 6. PMID: 37674002; PMCID: PMC10482689.

Onoja A, Picchiotti N, Fallerini C, Baldassarri M, Fava F; GEN-COVID Multicenter Study; Colombo F, Chiaromonte F, Renieri A, Furini S, Raimondi F. An explainable model of host genetic interactions linked to COVID-19 severity. Commun Biol. 2022 Oct 26;5(1):1133. doi: 10.1038/s42003-022-04073-6. PMID: 36289370; PMCID: PMC9606365.

Minnai F, De Bellis G, Dragani TA, Colombo F. COVID-19 mortality in Italy varies by patient age, sex and pandemic wave. Sci Rep. 2022 Mar 17;12(1):4604. doi: 10.1038/s41598-022-08573-7. PMID: 35301379; PMCID: PMC8929285.

Fallerini C, Picchiotti N, Baldassarri M, Zguro K, Daga S, Fava F, Benetti E, Amitrano S, Bruttini M, Palmieri M, Croci S, Lista M, Beligni G, Valentino F, Meloni I, Tanfoni M, Minnai F, Colombo F, Cabri E, Fratelli M, Gabbi C, Mantovani S, Frullanti E, Gori M, Crawley FP, Butler-Laporte G, Richards B, Zeberg H, Lipcsey M, Hultström M, Ludwig KU, Schulte EC, Pairo-Castineira E, Baillie JK, Schmidt A, Frithiof R; WES/WGS Working Group Within the HGI; GenOMICC Consortium; GEN-COVID Multicenter Study; Mari F, Renieri A, Furini S. Common, low-frequency, rare, and ultra-rare coding variants contribute to COVID-19 severity. Hum Genet. 2022 Jan;141(1):147-173. doi: 10.1007/s00439-021-02397-7. Epub 2021 Dec 10. PMID: 34889978; PMCID: PMC8661833.

Fallerini C, Daga S, Benetti E, Picchiotti N, Zguro K, Catapano F, Baroni V, Lanini S, Bucalossi A, Marotta G, Colombo F, Baldassarri M, Fava F, Beligni G, Di Sarno L, Alaverdian D, Palmieri M, Croci S, Isidori AM, Furini S, Frullanti E; GEN-COVID Multicenter Study; Renieri A, Mari F. SELP Asp603Asn and severe thrombosis in COVID-19 males. J Hematol Oncol. 2021 Aug 16;14(1):123. doi: 10.1186/s13045-021-01136-9. Erratum in: J Hematol Oncol. 2023 Feb 15;16(1):11. doi: 10.1186/s13045-023-01415-7. PMID: 34399825; PMCID: PMC8365289.

COVID-19 Host Genetics Initiative. Mapping the human genetic architecture of COVID-19. Nature. 2021 Dec;600(7889):472-477. doi: 10.1038/s41586-021-03767-x. Epub 2021 Jul 8. PMID: 34237774; PMCID: PMC8674144.

Cotroneo CE, Mangano N, Dragani TA, Colombo F. Lung expression of genes putatively involved in SARS-CoV-2 infection is modulated in cis by germline variants. Eur J Hum Genet. 2021 Jun;29(6):1019-1026. doi: 10.1038/s41431-021-00831-y. Epub 2021 Mar 1. PMID: 33649539; PMCID: PMC7917374.