Integrated immunovirological profiling validates plasma SARS-CoV-2 RNA as an early predictor of COVID-19 mortality

被引：34

作者：

Brunet-Ratnasingham, Elsa ^{[1
,2
]}

Anand, Sai Priya ^{[1
,3
]}

Gantner, Pierre ^{[1
,2
]}

Dyachenko, Alina ^{[1
]}

Moquin-Beaudry, Gael ^{[1
,4
]}

Brassard, Nathalie ^{[1
]}

Beaudoin-Bussieres, Guillaume ^{[1
,2
]}

Pagliuzza, Amelie ^{[1
]}

Gasser, Romain ^{[1
]}

Benlarbi, Mehdi ^{[1
]}

Point, Floriane ^{[1
]}

Prevost, Jeremie ^{[1
,2
]}

Laumaea, Annemarie ^{[1
]}

Niessl, Julia ^{[1
,2
,13
]}

Nayrac, Manon ^{[1
,2
]}

Sannier, Geremy ^{[1
,2
]}

Orban, Catherine ^{[2
,5
]}

Messier-Peet, Marc ^{[1
,5
]}

Butler-Laporte, Guillaume ^{[6
,7
]}

Morrison, David R. ^{[6
]}

Zhou, Sirui ^{[6
,7
]}

Nakanishi, Tomoko ^{[6
,8
,9
,10
]}

Boutin, Marianne ^{[1
,2
]}

Descoteaux-Dinelle, Jade ^{[1
,2
]}

Gendron-Lepage, Gabrielle ^{[1
]}

Goyette, Guillaume ^{[1
]}

Bourassa, Catherine ^{[1
]}

Medjahed, Halima ^{[1
]}

Laurent, Laetitia ^{[6
]}

Rebillard, Rose-Marie ^{[1
,4
]}

Richard, Jonathan ^{[1
,2
]}

Dube, Mathieu ^{[1
]}

Fromentin, Remi ^{[1
]}

Arbour, Nathalie ^{[1
,4
]}

Prat, Alexandre ^{[1
,4
]}

Larochelle, Catherine ^{[1
,4
]}

Durand, Madeleine ^{[1
,5
]}

Richards, J. Brent ^{[6
,7
,8
,11
]}

Chasse, Michael ^{[1
,5
]}

Tetreault, Martine ^{[1
,4
]}

Chomont, Nicolas ^{[1
,2
]}

Finzi, Andres ^{[1
,2
,3
]}

Kaufmann, Daniel E. ^{[1
,2
,5
,12
]}

机构：

[1] Ctr Hosp Univ Montreal CRCHUM, Res Ctr, Montreal, PQ, Canada

[2] Univ Montreal, Dept Microbiol Infectiol & Immunol, Montreal, PQ, Canada

[3] McGill Univ, Dept Microbiol & Immunol, Montreal, PQ, Canada

[4] Univ Montreal, Dept Neurosci, Montreal, PQ, Canada

[5] Ctr Hosp Univ Montreal CHUM, Montreal, PQ, Canada

[6] McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada

[7] McGill Univ, Dept Epidemiol Biostat & Occupat Hlth, Montreal, PQ, Canada

[8] McGill Univ, Dept Human Genet, Montreal, PQ, Canada

[9] Kyoto Univ, Grad Sch Med, Kyoto McGill Int Collaborat Sch Genom Med, Kyoto, Japan

[10] Japan Soc Promot Sci, Chiyoda Ku, 5-3-1 Kojimachi, Tokyo 1020083, Japan

[11] Kings Coll London, Dept Twin Res, London, England

[12] Univ Montreal, Dept Med, Montreal, PQ, Canada

[13] Karolinska Inst, Ctr Infect Med, Dept Med Huddinge, Stockholm, Sweden

来源：

SCIENCE ADVANCES | 2021年 / 7卷 / 48期

基金：

加拿大创新基金会; 加拿大健康研究院;

关键词：

VIRAL-RNA; ANGIOPOIETIN-2; CORONAVIRUS; ANTIBODIES; SURVIVAL; DISEASE; BLOOD; CELLS;

D O I：

10.1126/sciadv.abj5629

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Despite advances in COVID-19 management, identifying patients evolving toward death remains challenging. To identify early predictors of mortality within 60 days of symptom onset (DSO), we performed immunovirological assessments on plasma from 279 individuals. On samples collected at DSO11 in a discovery cohort, high severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral RNA (vRNA), low receptor binding domain-specific immunoglobulin G and antibody-dependent cellular cytotoxicity, and elevated cytokines and tissue injury markers were strongly associated with mortality, including in patients on mechanical ventilation. A three-variable model of vRNA, with predefined adjustment by age and sex, robustly identified patients with fatal outcome (adjusted hazard ratio for log-transformed vRNA = 3.5). This model remained robust in independent validation and confirmation cohorts. Since plasma vRNA's predictive accuracy was maintained at earlier time points, its quantitation can help us understand disease heterogeneity and identify patients who may benefit from new therapies.

引用

页数：16

共 66 条

[1] Longitudinal analysis of humoral immunity against SARS-CoV-2 Spike in convalescent individuals up to 8 months post-symptom onset [J].

Anand, Sai Priya ;

Prevost, Jeremie ;

Nayrac, Manon ;

Beaudoin-Bussieres, Guillaume ;

Benlarbi, Mehdi ;

Gasser, Romain ;

Brassard, Nathalie ;

Laumaea, Annemarie ;

Gong, Shang Yu ;

Bourassa, Catherine ;

Brunet-Ratnasingham, Elsa ;

Medjahed, Halima ;

Gendron-Lepage, Gabrielle ;

Goyette, Guillaume ;

Gokool, Laurie ;

Morrisseau, Chantal ;

Begin, Philippe ;

Martel-Laferriere, Valerie ;

Tremblay, Cecile ;

Richard, Jonathan ;

Bazin, Renee ;

Duerr, Ralf ;

Kaufmann, Daniel E. ;

Finzi, Andres .

CELL REPORTS MEDICINE, 2021, 2 (06)

[2] Systems biological assessment of immunity to mild versus severe COVID-19 infection in humans [J].

Arunachalam, Prabhu S. ;

Wimmers, Florian ;

Mok, Chris Ka Pun ;

Perera, Ranawaka A. P. M. ;

Scott, Madeleine ;

Hagan, Thomas ;

Sigal, Natalia ;

Feng, Yupeng ;

Bristow, Laurel ;

Tsang, Owen Tak-Yin ;

Wagh, Dhananjay ;

Coller, John ;

Pellegrini, Kathryn L. ;

Kazmin, Dmitri ;

Alaaeddine, Ghina ;

Leung, Wai Shing ;

Chan, Jacky Man Chun ;

Chik, Thomas Shiu Hong ;

Choi, Chris Yau Chung ;

Huerta, Christopher ;

McCullough, Michele Paine ;

Lv, Huibin ;

Anderson, Evan ;

Edupuganti, Srilatha ;

Upadhyay, Amit A. ;

Bosinger, Steve E. ;

Maecker, Holden Terry ;

Khatri, Purvesh ;

Rouphael, Nadine ;

Peiris, Malik ;

Pulendran, Bali .

SCIENCE, 2020, 369 (6508) :1210-+

[3] Distinct Early Serological Signatures Track with SARS-CoV-2 Survival [J].

Atyeo, Caroline ;

Fischinger, Stephanie ;

Zohar, Tomer ;

Slein, Matthew D. ;

Burke, John ;

Loos, Carolin ;

McCulloch, Denise J. ;

Newman, Kira L. ;

Wolf, Caitlin ;

Yu, Jingyou ;

Shuey, Kiel ;

Feldman, Jared ;

Hauser, Blake Marie ;

Caradonna, Tim ;

Schmidt, Aaron G. ;

Suscovich, Todd J. ;

Linde, Caitlyn ;

Cai, Yongfei ;

Barouch, Dan ;

Ryan, Edward T. ;

Charles, Richelle C. ;

Lauffenburger, Douglas ;

Chu, Helen ;

Alter, Galit .

IMMUNITY, 2020, 53 (03) :524-+

[4]

Beaudoin-Bussieres G., 2021, STAR PROTOC, V2

[5] Decline of Humoral Responses against SARS-CoV-2 Spike in Convalescent Individuals [J].

Beaudoin-Bussieres, Guillaume ;

Laumaea, Annemarie ;

Anand, Sai Priya ;

Prevost, Jeremie ;

Gasser, Romain ;

Goyette, Guillaume ;

Medjahed, Halima ;

Perreault, Josee ;

Tremblay, Tony ;

Lewin, Antoine ;

Gokool, Laurie ;

Morrisseau, Chantal ;

Begin, Philippe ;

Tremblay, Cecile ;

Martel-Laferriere, Valerie ;

Kaufmann, Daniel E. ;

Richard, Jonathan ;

Bazin, Renee ;

Finzi, Andres .

MBIO, 2020, 11 (05) :1-7

[6]

Beigel JH, 2020, NEW ENGL J MED, V383, P1813, DOI [10.1056/NEJMoa2007764, 10.1056/NEJMc2022236]

[7] Severe Covid-19 [J].

Berlin, David A. ;

Gulick, Roy M. ;

Martinez, Fernando J. .

NEW ENGLAND JOURNAL OF MEDICINE, 2020, 383 (25) :2451-2460

[8]

Blanche L. A., 2013, LECT NOTES STAT, V215

[9] Survival Analysis Part II: Multivariate data analysis - an introduction to concepts and methods [J].

Bradburn, MJ ;

Clark, TG ;

Love, SB ;

Altman, DG .

BRITISH JOURNAL OF CANCER, 2003, 89 (03) :431-436

[10] Nonlinear Imputation of Pao2/Fio2 From Spo2/Fio2 Among Mechanically Ventilated Patients in the ICU: A Prospective, Observational Study [J].

Brown, Samuel M. ;

Duggal, Abhijit ;

Hou, Peter C. ;

Tidswell, Mark ;

Khan, Akram ;

Exline, Matthew ;

Park, Pauline K. ;

Schoenfeld, David A. ;

Liu, Ming ;

Grissom, Colin K. ;

Moss, Marc ;

Rice, Todd W. ;

Hough, Catherine L. ;

Rivers, Emanuel ;

Thompson, B. Taylor ;

Brower, Roy G. .

CRITICAL CARE MEDICINE, 2017, 45 (08) :1317-1324

← 1 2 3 4 5 6 7 →