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Data availability
The dataset for 332 COVID-19 patients is publicly available at the European Bioinformatics Institute (www.ebi.ac.uk/gwas) under accession nos. GCST90000255 and GCST90000256 (ref. 6), whereas the dataset for 1,668 healthy individuals of the general population is deposited in the Genotypes and Phenotypes database (https://www.ncbi.nlm.nih.gov/gap) under accession no. phs000294.v1.p1 (ref. 7). As for the remaining 195 patients and 1,522 controls, data are available from the corresponding author on reasonable request, until their publication in a public repository (pending the acceptance of an unrelated manuscript)10. Data related to the analyzed MBL2 locus are available at (https://doi.org/10.5281/zenodo.6452010).
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Acknowledgements
This work was conducted in the framework of, and made possible by, the collective effort of the Humanitas COVID-19 Task Force, the Humanitas Gavazzeni COVID-19 Task Force and the COVID-19 Storm trial. This paper is dedicated to S. Duga, who passed on 10 November 2021 and had made a key contribution to the genetic section of this report. This work was supported by a philanthropic donation by Dolce & Gabbana fashion house (to A.M. and C.G.), by the Italian Ministry of Health for COVID-19 (grant no. COVID-2020-12371640 to A.M. and C.G.), by the Italian Ministry of University and Research (to P.I.), by the Department of Excellence project PREMIA (PREcision MedIcine Approach: bringing biomarker research to the clinic, to P.I.) and by Fondazione Cariplo (Biobanking of COVID-19 patient samples to support national and international research, to A.B.). We also thank the Banca Intesa San Paolo for their generous contribution (to R.A.) and AMAF Monza ONLUS and AIRCS for unrestricted research funding. L.V. received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement no. 101003650 and from the Swiss National Science Foundation (grant no. 31003A_182270).
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Contributions
A.M., C.G. and R.A. conceived this extension of the original study reported in ref. 1. M.S. conducted the experimental work related to binding and complement activation. The genetic analysis was conducted by E.M.P. R.A. supervised the analysis. P.I., P.B. and A.B. provided samples for the genetic analysis. All authors contributed to project design and planning, data analysis and interpretation.
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A.M., C.G. and B.B. are inventors of a patent (EP20182181) on PTX3 and obtain royalties on related reagents. A.M., C.G., B.B. and E.V. are inventors of two patents (102021000002738 and EP21214373.9) on MBL. R.R. is a full-time employee of the GSK group of companies. The other authors declare no competing interests.
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Nature Immunology thanks the anonymous reviewers for their contribution to the peer review of this work.
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Extended data
Extended Data Fig. 1 The MBL2 locus: structure and main association signals with severe COVID-19.
A screenshot from the UCSC Genome browser (http://genome.ucsc.edu/; release Dec. 2013, GRCh38/hg38) specifically highlighting the 1-Mb region surrounding the MBL2 gene is shown. The panel reports, in order, the following tracks: i) the ruler with the scale at the genomic level; ii) chromosome 10 nucleotide numbering; iii) the UCSC RefSeq track; iv) COVID-19 risk variants from the COVID-19 HGI GWAS Analysis A2 (8,779 cases, 25 studies, Release 6: June 2021); v) COVID-19 risk variants from the COVID-19 HGI GWAS Analysis B2 (24,274 cases, 43 studies, Release 6: June 2021); vi) COVID-19 risk variants from the COVID-19 HGI GWAS Analysis C2 (112,612 cases, 74 studies, Release 6: June 2021); vii) COVID-19 risk haplotypes, marked by the tagging SNP, from our larger study (lollipops show all haplotypes reported in Table 2). All panels reporting COVID-19 risk variants from the COVID-19 HGI GWAS analysis show only signals at P < 5 × 10−3; the lollipop height and color depends on the -log10(P): dark pink indicates P < 10-4, orange indicates 10−4 < P < 10−3, light pink indicates 10−3 < P < 5 × 10−3.
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Asselta, R., Paraboschi, E.M., Stravalaci, M. et al. Reply to: Hultström et al., Genetic determinants of mannose-binding lectin activity predispose to thromboembolic complications in critical COVID-19. Mannose-binding lectin genetics in COVID-19. Nat Immunol 23, 865–867 (2022). https://doi.org/10.1038/s41590-022-01228-9
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DOI: https://doi.org/10.1038/s41590-022-01228-9
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