Contribution of Coronavirus-Specific Immunoglobulin G Responses to Complement Overactivation in Patients with Severe Coronavirus Disease 2019

被引：13

作者：

Castanha, Priscila M. S. ^{[1
]}

Tuttle, Dylan J. ^{[1
]}

Kitsios, Georgios D. ^{[2
,3
,4
]}

Jacobs, Jana L. ^{[5
]}

Braga-Neto, Ulisses ^{[6
]}

Duespohl, Matthew ^{[1
]}

Rathod, Sanjay ^{[7
]}

Marti, Michelle M. ^{[1
]}

Wheeler, Sarah ^{[8
]}

Naqvi, Asma ^{[5
]}

Staines, Brittany ^{[5
]}

Mellors, John ^{[5
]}

Morris, Alison ^{[2
,4
]}

McVerry, Bryan J. ^{[2
,3
,4
]}

Shah, Faraaz ^{[3
]}

Schaefer, Caitlin ^{[2
]}

Macatangay, Bernard J. C. ^{[5
]}

Methe, Barbara ^{[2
,4
]}

Fernandez, Christian A. ^{[7
]}

Barratt-Boyes, Simon M. ^{[1
,9
]}

Burke, Donald ^{[10
]}

Marques, Ernesto T. A. ^{[1
]}

机构：

[1] Univ Pittsburgh, Dept Infect Dis & Microbiol, Pittsburgh, PA 15261 USA

[2] Univ Pittsburgh, Dept Med, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA 15261 USA

[3] Univ Pittsburgh, Dept Med, Acute Lung Injury Ctr Excellence, Pittsburgh, PA 15261 USA

[4] Univ Pittsburgh, Dept Med, Ctr Med & Microbiome, Pittsburgh, PA 15261 USA

[5] Univ Pittsburgh, Dept Med, Div Infect Dis, Pittsburgh, PA 15261 USA

[6] Texas A&M Univ, Coll Architecture, Dept Elect & Comp Engn, College Stn, TX 77843 USA

[7] Univ Pittsburgh, Ctr Pharmacogenet, Dept Pharmaceut Sci, Pittsburgh, PA 15261 USA

[8] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA 15261 USA

[9] Univ Pittsburgh, Dept Immunol, Pittsburgh, PA 15261 USA

[10] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA

来源：

JOURNAL OF INFECTIOUS DISEASES | 2022年 / 226卷 / 05期

基金：

美国国家卫生研究院;

关键词：

SARS-CoV-2; COVID-19; complement system; classical pathway; common cold coronaviruses; and antibodies; SARS-COV-2;

D O I：

10.1093/infdis/jiac091

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Our findings reveal that complement overactivation is mediated by the classical pathway in response to increased levels of circulating immune complexes and support the notion that an overexuberant immunoglobulin G response against severe acute respiratory syndrome coronavirus 2 and seasonal coronaviruses contributes to coronavirus disease 2019 severity. Background Excessive complement activation has been implicated in the pathogenesis of coronavirus disease 2019 (COVID-19), but the mechanisms leading to this response remain unclear. Methods We measured plasma levels of key complement markers, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA and antibodies against SARS-CoV-2 and seasonal human common cold coronaviruses (CCCs) in hospitalized patients with COVID-19 of moderate (n = 18) and critical severity (n = 37) and in healthy controls (n = 10). Results We confirmed that complement activation is systemically increased in patients with COVID-19 and is associated with a worse disease outcome. We showed that plasma levels of C1q and circulating immune complexes were markedly increased in patients with severe COVID-19 and correlated with higher immunoglobulin (Ig) G titers, greater complement activation, and higher disease severity score. Additional analyses showed that the classical pathway was the main arm responsible for augmented complement activation in severe patients. In addition, we demonstrated that a rapid IgG response to SARS-CoV-2 and an anamnestic IgG response to the nucleoprotein of the CCCs were strongly correlated with circulating immune complex levels, complement activation, and disease severity. Conclusions These findings indicate that early, nonneutralizing IgG responses may play a key role in complement overactivation in severe COVID-19. Our work underscores the urgent need to develop therapeutic strategies to modify complement overactivation in patients with COVID-19.

引用

页码：766 / 777

页数：12

共 48 条

[1] Seasonal coronavirus-specific B cells with limited SARS-CoV-2 cross-reactivity dominate the IgG response in severe COVID-19 [J].

Aguilar-Bretones, Muriel ;

Westerhuis, Brenda M. ;

Raadsen, Matthijs P. ;

de Bruin, Erwin ;

Chandler, Felicity D. ;

Okba, Nisreen M. A. ;

Haagmans, Bart L. ;

Langerak, Thomas ;

Endeman, Henrik ;

van den Akker, Johannes P. C. ;

Gommers, Diederik A. M. P. J. ;

van Gorp, Eric C. M. ;

GeurtsvanKessel, Corine H. ;

de Vries, Rory D. ;

Fouchier, Ron A. M. ;

Rockx, Barry H. G. ;

Koopmans, Marion P. G. ;

van Nierop, Gijsbert P. .

JOURNAL OF CLINICAL INVESTIGATION, 2021, 131 (21)

[2] Lectin Pathway Mediates Complement Activation by SARS-CoV-2 Proteins [J].

Ali, Youssif M. ;

Ferrari, Matteo ;

Lynch, Nicholas J. ;

Yaseen, Sadam ;

Dudler, Thomas ;

Gragerov, Sasha ;

Demopulos, Gregory ;

Heeney, Jonathan L. ;

Schwaeble, Wilhelm J. .

FRONTIERS IN IMMUNOLOGY, 2021, 12

[3] Complement Anaphylatoxins and Inflammatory Cytokines as Prognostic Markers for COVID-19 Severity and In-Hospital Mortality [J].

Alosaimi, Bandar ;

Mubarak, Ayman ;

Hamed, Maaweya E. ;

Almutairi, Abdullah Z. ;

Alrashed, Ahmed A. ;

AlJuryyan, Abdullah ;

Enani, Mushira ;

Alenzi, Faris Q. ;

Alturaiki, Wael .

FRONTIERS IN IMMUNOLOGY, 2021, 12

[4] Seasonal human coronavirus antibodies are boosted upon SARS-CoV-2 infection but not associated with protection [J].

Anderson, Elizabeth M. ;

Goodwin, Eileen C. ;

Verma, Anurag ;

Arevalo, Claudia P. ;

Bolton, Marcus J. ;

Weirick, Madison E. ;

Gouma, Sigrid ;

McAllister, Christopher M. ;

Christensen, Shannon R. ;

Weaver, JoEllen ;

Hicks, Philip ;

Manzoni, Tomaz B. ;

Oniyide, Oluwatosin ;

Ramage, Holly ;

Mathew, Divij ;

Baxter, Amy E. ;

Oldridge, Derek A. ;

Greenplate, Allison R. ;

Wu, Jennifer E. ;

Alanio, Cecile ;

D'Andrea, Kurt ;

Kuthuru, Oliva ;

Dougherty, Jeanette ;

Pattekar, Ajinkya ;

Kim, Justin ;

Han, Nicholas ;

Apostolidis, Sokratis A. ;

Huang, Alex C. ;

Vella, Laura A. ;

Kuri-Cervantes, Leticia ;

Pampena, M. Betina ;

Betts, Michael R. ;

Wherry, E. John ;

Meyer, Nuala J. ;

Cherry, Sara ;

Bates, Paul ;

Rader, Daniel J. ;

Hensley, Scott E. .

CELL, 2021, 184 (07) :1858-+

[5]

Ankerhold J, 2021, bioRxiv, DOI [10.1101/2021.06.25.449893, 10.1101/2021.06.25.449893, DOI 10.1101/2021.06.25.449893]

[6] Immunological imprinting of the antibody response in COVID-19 patients [J].

Aydillo, Teresa ;

Rombauts, Alexander ;

Stadlbauer, Daniel ;

Aslam, Sadaf ;

Abelenda-Alonso, Gabriela ;

Escalera, Alba ;

Amanat, Fatima ;

Jiang, Kaijun ;

Krammer, Florian ;

Carratala, Jordi ;

Garcia-Sastre, Adolfo .

NATURE COMMUNICATIONS, 2021, 12 (01)

[7] COVID-19 versus Non-COVID-19 Acute Respiratory Distress Syndrome Comparison of Demographics, Physiologic Parameters, Inflammatory Biomarkers, and Clinical Outcomes [J].

Bain, William ;

Yang, Haopu ;

Shah, Faraaz Ali ;

Suber, Tomeka ;

Drohan, Callie ;

Al-Yousif, Nameer ;

DeSensi, Rebecca S. ;

Bensen, Nicole ;

Schaefer, Caitlin ;

Rosborough, Brian R. ;

Somasundaram, Ashwin ;

Workman, Creg J. ;

Lampenfeld, Caleb ;

Cillo, Anthony R. ;

Cardello, Carly ;

Shan, Feng ;

Bruno, Tullia C. ;

Vignali, Dario A. A. ;

Ray, Prabir ;

Ray, Anuradha ;

Zhang, Yingze ;

Lee, Janet S. ;

Methe, Barbara ;

McVerry, Bryan J. ;

Morris, Alison ;

Kitsios, Georgios D. .

ANNALS OF THE AMERICAN THORACIC SOCIETY, 2021, 18 (07) :1202-1210

[8] Increased Alternative Complement Pathway Function and Improved Survival during Critical Illness [J].

Bain, William ;

Li, Huihua ;

van der Geest, Rick ;

Moore, Sara R. ;

Olonisakin, Tolani F. ;

Ahn, Brian ;

Papke, Erin ;

Moghbeli, Kaveh ;

DeSensi, Rebecca ;

Rapport, Sarah ;

Saul, Melissa ;

Hulver, Mei ;

Xiong, Zeyu ;

Mallampalli, Rama K. ;

Ray, Prabir ;

Morris, Alison ;

Ma, Lina ;

Doi, Yohei ;

Zhang, Yingze ;

Kitsios, Georgios D. ;

Kulkarni, Hrishikesh S. ;

McVerry, Bryan J. ;

Ferreira, Viviana P. ;

Nouraie, Mehdi ;

Lee, Janet S. .

AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2020, 202 (02) :230-240

[9] Viral RNA load in plasma is associated with critical illness and a dysregulated host response in COVID-19 [J].

Bermejo-Martin, Jesus F. ;

Gonzalez-Rivera, Milagros ;

Almansa, Raquel ;

Micheloud, Dariela ;

Tedim, Ana P. ;

Dominguez-Gil, Marta ;

Resino, Salvador ;

Martin-Fernandez, Marta ;

Ryan Murua, Pablo ;

Perez-Garcia, Felipe ;

Tamayo, Luis ;

Lopez-Izquierdo, Raul ;

Bustamante, Elena ;

Aldecoa, Cesar ;

Manuel Gomez, Jose ;

Rico-Feijoo, Jesus ;

Orduna, Antonio ;

Mendez, Raul ;

Fernandez Natal, Isabel ;

Megias, Gregoria ;

Gonzalez-Estecha, Montserrat ;

Carriedo, Demetrio ;

Doncel, Cristina ;

Jorge, Noelia ;

Ortega, Alicia ;

de la Fuente, Amanda ;

del Campo, Felix ;

Antonio Fernandez-Ratero, Jose ;

Trapiello, Wysali ;

Gonzalez-Jimenez, Paula ;

Ruiz, Guadalupe ;

Kelvin, Alyson A. ;

Ostadgavahi, Ali Toloue ;

Oneizat, Ruth ;

Maria Ruiz, Luz ;

Miguens, Iria ;

Gargallo, Esther ;

Munoz, Ioana ;

Pelegrin, Sara ;

Martin, Silvia ;

Garcia Olivares, Pablo ;

Antonio Cedeno, Jamil ;

Ruiz Albi, Tomas ;

Puertas, Carolina ;

Angel Berezo, Jose ;

Renedo, Gloria ;

Herran, Ruben ;

Bustamante-Munguira, Juan ;

Enriquez, Pedro ;

Cicuendez, Ramon .

CRITICAL CARE, 2020, 24 (01)

[10]

Braga-Neto UM., 2004, ERROR ESTIMATION PAT

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