Compromised Humoral Functional Evolution Tracks with SARS-CoV-2 Mortality

被引：227

作者：

Zohar, Tomer ^{[1
,2
]}

Loos, Carolin ^{[1
,2
]}

Fischinger, Stephanie ^{[1
,3
]}

Atyeo, Caroline ^{[1
,4
]}

Wang, Chuangqi ^{[2
]}

Slein, Matthew D. ^{[1
]}

Burke, John ^{[1
]}

Yu, Jingyou ^{[5
]}

Feldman, Jared ^{[1
]}

Hauser, Blake Marie ^{[1
]}

Caradonna, Tim ^{[1
]}

Schmidt, Aaron G. ^{[1
]}

Cai, Yongfei ^{[6
,7
]}

Streeck, Hendrik ^{[8
,9
]}

Ryan, Edward T. ^{[10
]}

Barouch, Dan H. ^{[5
]}

Charles, Richelle C. ^{[10
]}

Lauffenburger, Douglas A. ^{[2
]}

Alter, Galit ^{[1
]}

机构：

[1] Ragon Inst MGH MIT & Harvard, Cambridge, MA 02138 USA

[2] MIT, Dept Biol Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA

[3] Univ Duisburg Essen, PhD Program Immunol & Virol, Essen, Germany

[4] Harvard Univ, PhD Program Virol, Div Med Sci, Boston, MA 02115 USA

[5] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Ctr Virol & Vaccine Res, Boston, MA 02215 USA

[6] Harvard Med Sch, Div Mol Med, Boston Childrens Hosp, Boston, MA 02115 USA

[7] Harvard Med Sch, Dept Pediat, Boston, MA 02115 USA

[8] Univ Bonn, Univ Hosp, Inst Virol, Bonn, Germany

[9] German Ctr Infect Res DZIF, Bonn, Germany

[10] Harvard Med Sch, Massachusetts Gen Hosp, Lnfectious Dis Div, Boston, MA 02215 USA

来源：

CELL | 2020年 / 183卷 / 06期

关键词：

EFFECTOR FUNCTIONS; PERMUTATION TESTS; HIGH-THROUGHPUT; ANTIBODIES; IMMUNITY; SYSTEMS; ROBUST;

D O I：

10.1016/j.cell.2020.10.052

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The urgent need for an effective SARS-CoV-2 vaccine has forced development to progress in the absence of well-defined correlates of immunity. While neutralization has been linked to protection against other pathogens, whether neutralization alone will be sufficient to drive protection against SARS-CoV-2 in the broader population remains unclear Therefore, to fully define protective humoral immunity, we dissected the early evolution of the humoral response in 193 hospitalized individuals ranging from moderate to severe. Although robust IgM and IgA responses evolved in both survivors and non-survivors with severe disease, non-survivors showed attenuated IgG responses, accompanied by compromised Fcv receptor binding and Fc effector activity, pointing to deficient humoral development rather than disease-enhancing humoral immunity. In contrast, individuals with moderate disease exhibited delayed responses that ultimately matured. These data highlight distinct humoral trajectories associated with resolution of SARS-CoV-2 infection and the need for early functional humoral immunity.

引用

页码：1508 / +

页数：24

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