Stratification of hospitalized COVID-19 patients into clinical severity progression groups by immuno-phenotyping and machine learning.
Yvonne M MuellerThijs J SchramaRik RuijtenMarco W J SchreursDwin G B GrashofHarmen J G van de WerkenGiovanna Jona LasinioDaniel Alvarez-SierraCaoimhe H KiernanMelisa Daiana Castro EiroMarjan van MeursInge Brouwers-HaspelsManzhi ZhaoLing LiHarm de WitChristos A OuzounisMerel E P WilmsenTessa M AlofsDanique A LaportTamara van WeesGeoffrey KrakerMaria C JaimesSebastiaan Van BockstaelManuel Hernández-GonzálezCasper RokxBart J A RijndersRicardo Pujol-BorrellPeter D KatsikisPublished in: Nature communications (2022)
Quantitative or qualitative differences in immunity may drive clinical severity in COVID-19. Although longitudinal studies to record the course of immunological changes are ample, they do not necessarily predict clinical progression at the time of hospital admission. Here we show, by a machine learning approach using serum pro-inflammatory, anti-inflammatory and anti-viral cytokine and anti-SARS-CoV-2 antibody measurements as input data, that COVID-19 patients cluster into three distinct immune phenotype groups. These immune-types, determined by unsupervised hierarchical clustering that is agnostic to severity, predict clinical course. The identified immune-types do not associate with disease duration at hospital admittance, but rather reflect variations in the nature and kinetics of individual patient's immune response. Thus, our work provides an immune-type based scheme to stratify COVID-19 patients at hospital admittance into high and low risk clinical categories with distinct cytokine and antibody profiles that may guide personalized therapy.