{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T05:00:18Z","timestamp":1781154018150,"version":"3.54.1"},"reference-count":59,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T00:00:00Z","timestamp":1781136000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>The first wave of Coronavirus disease 2019 (COVID-19), driven by the global emergence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), severely affected Spain with high infection and mortality rates across the country. Although numerous common and rare genetic variants affecting immune-related pathways have been associated with susceptibility to infection and severe disease, the contribution of complement system remains comparatively understudied.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this work, we analyzed the frequencies and severity associations of complotype-related common polymorphisms and rare complement variants in whole-exome sequencing data from a Spanish cohort accounting for 154 adults hospitalized due to severe COVID-19.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Our results indicate that the\n                      <jats:italic>CFHR4<\/jats:italic>\n                      rs7417769 (p.N209S) and CFH\n                      <jats:italic>rs1061170<\/jats:italic>\n                      (p. Y402H) common polymorphisms are significantly associated with protection against acute respiratory distress syndrome (ARDS), while the\n                      <jats:italic>C3<\/jats:italic>\n                      rs2230199 (p.R102G) and\n                      <jats:italic>MASP2<\/jats:italic>\n                      rs7255087 (p.D120G) polymorphisms respectively correlated with low and high\n                      <jats:italic>C3<\/jats:italic>\n                      levels. The marked over-representation of the\n                      <jats:italic>C1R<\/jats:italic>\n                      rs117402032 and\n                      <jats:italic>C8A<\/jats:italic>\n                      rs143523574 polymorphisms and increased frequency of heterozygous carriers of alleles previously associated with low FCN2 and FCN3 levels, suggest a link beween defective complement activation and increased rates of SARS-CoV-2 infection and support a pivotal role for the lectin pathway in the pathogenesis of COVID-19.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Together, these results demonstrate that common variants in complement genes modulate susceptibility to severe COVID-19 and its clinical complications. They also identify promising, testable genetic biomarkers with potential utility not only for SARS-CoV-2, but also for preparedness against future emerging infectious threats.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1829115","type":"journal-article","created":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T04:39:54Z","timestamp":1781152794000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Common and rare variants in complement genes as biomarkers of COVID-19 infection and severity. 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