Robust Neutralizing Antibodies to SARS-CoV-2 Develop and Persist in Subjects with Diabetes and COVID-19 Pneumonia

被引:38
作者
Dispinseri, Stefania [1 ]
Lampasona, Vito [2 ]
Secchi, Massimiliano [2 ]
Cara, Andrea [3 ]
Bazzigaluppi, Elena [2 ]
Negri, Donatella [4 ]
Brigatti, Cristina [2 ]
Pirillo, Maria Franca [3 ]
Marzinotto, Ilaria [2 ]
Borghi, Martina [4 ]
Rovere-Querini, Patrizia [5 ,6 ]
Tresoldi, Cristina [7 ]
Ciceri, Fabio [6 ,8 ]
Scavini, Marina [2 ]
Scarlatti, Gabriella [1 ]
Piemonti, Lorenzo [2 ,6 ]
机构
[1] IRCCS Osped San Raffaele, Viral Evolut & Trasmiss Unit, Milan, Italy
[2] IRCCS Osped San Raffaele, Diabet Res Inst, Milan, Italy
[3] Ist Super Sanita, Natl Ctr Global Hlth, Rome, Italy
[4] Ist Super Sanita, Dept Infect Dis, Rome, Italy
[5] IRCCS Osped San Raffaele, Dept Immunol Transplantat & Infect Dis, Milan, Italy
[6] Univ Vita Salute San Raffaele, Sch Med & Surg, Milan, Italy
[7] IRCCS Osped San Raffaele, Mol Hematol Unit, Milan, Italy
[8] IRCCS Osped San Raffaele, Hematol & Bone Marrow Transplantat Unit, Milan, Italy
关键词
neutralizing antibodies; COVID-19; diabetes; survival rate; humoral response; SARS-CoV-2; CLINICAL CHARACTERISTICS; NONENZYMATIC GLYCATION; VACCINE; MELLITUS;
D O I
10.1210/clinem/dgab055
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Context: Demonstrating the ability to mount a neutralizing antibody response to SARS-CoV-2 in the presence of diabetes is crucial to understand COVID-19 pathogenesis, reinfection potential, and vaccine development. Objective: The aim of this study was to characterize the kinetics and durability of neutralizing antibody (Nab) response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the presence of hyperglycemia. Methods: Using a lentiviral vector-based SARS-CoV-2 neutralization assay to measure Nabs, we characterized 150 patients randomly selected from a cohort of 509 patients with confirmed COVID-19 pneumonia. We analyzed Nab response according to the presence of diabetes or hyperglycemia, at the time of hospitalization and during the postdischarge follow-up: 1-, 3-, and 6-month outpatient visits. Results: Among 150 randomly selected patients 40 (26.6%) had diabetes. Diabetes (hazard ratio [HR] 8.9, P <.001), glucose levels (HR 1.25 x 1.1 mmol/L, P <.001), and glucose variability (HR 1.17 x 0.6 mmol/L, P <.001) were independently associated with an increased risk of mortality. The neutralizing activity of SARS-CoV-2 antibodies in patients with diabetes was superimposable, as for kinetics and extent, to that of patients without diabetes. It was similar across glucose levels and correlated with the humoral response against the SARS-CoV-2 spike protein. Positivity for Nabs at the time of hospital admission conferred protection on mortality, both in the presence (HR 0.28, P =.046) or absence of diabetes (HR 0.26, P =.030). The longevity of the Nab response was not affected by diabetes. Conclusion: Diabetes and hyperglycemia do not affect the kinetics and durability of the neutralizing antibody response to SARS-CoV-2. These findings provide the rational to include patients with diabetes in the early phase of the vaccination campaign against SARS-CoV-2.
引用
收藏
页码:1472 / 1481
页数:10
相关论文
共 48 条
[1]   The role of IgG Fc receptors in antibody-dependent enhancement [J].
Bournazos, Stylianos ;
Gupta, Aaron ;
Ravetch, Jeffrey, V .
NATURE REVIEWS IMMUNOLOGY, 2020, 20 (10) :633-643
[2]   Early predictors of clinical outcomes of COVID-19 outbreak in Milan, Italy [J].
Ciceri, Fabio ;
Castagna, Antonella ;
Rovere-Querini, Patrizia ;
De Cobelli, Francesco ;
Ruggeri, Annalisa ;
Galli, Laura ;
Conte, Caterina ;
De Lorenzo, Rebecca ;
Poli, Andrea ;
Ambrosio, Alberto ;
Signorelli, Carlo ;
Bossi, Eleonora ;
Fazio, Maria ;
Tresoldi, Cristina ;
Colombo, Sergio ;
Monti, Giacomo ;
Fominskiy, Efgeny ;
Franchini, Stefano ;
Spessot, Marzia ;
Martinenghi, Carlo ;
Carlucci, Michele ;
Beretta, Luigi ;
Scandroglio, Anna Maria ;
Clementi, Massimo ;
Locatelli, Massimo ;
Tresoldi, Moreno ;
Scarpellini, Paolo ;
Martino, Gianvito ;
Bosi, Emanuele ;
Dagna, Lorenzo ;
Lazzarin, Adriano ;
Landoni, Giovanni ;
Zangrillo, Alberto .
CLINICAL IMMUNOLOGY, 2020, 217
[3]   Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection [J].
Dan, Jennifer M. ;
Mateus, Jose ;
Kato, Yu ;
Hastie, Kathryn M. ;
Yu, Esther Dawen ;
Faliti, Caterina E. ;
Grifoni, Alba ;
Ramirez, Sydney, I ;
Haupt, Sonya ;
Frazier, April ;
Nakao, Catherine ;
Rayaprolu, Vamseedhar ;
Rawlings, Stephen A. ;
Peters, Bjoern ;
Krammer, Florian ;
Simon, Viviana ;
Saphire, Erica Ollmann ;
Smith, Davey M. ;
Weiskopf, Daniela ;
Sette, Alessandro ;
Crotty, Shane .
SCIENCE, 2021, 371 (6529) :587-+
[4]   Positive results for patients with COVID-19 discharged form hospital in Chongqing, China [J].
Deng, Wang ;
Guang, Tian-wen ;
Yang, Mei ;
Li, Jian-rong ;
Jiang, De-peng ;
Li, Chang-yi ;
Wang, Dao-xin .
BMC INFECTIOUS DISEASES, 2020, 20 (01)
[5]   The immuno-oncological challenge of COVID-19 [J].
Derosa, Lisa ;
Melenotte, Clea ;
Griscelli, Franck ;
Gachot, Bertrand ;
Marabelle, Aurelien ;
Kroemer, Guido ;
Zitvogel, Laurence .
NATURE CANCER, 2020, 1 (10) :946-964
[6]   Increased Expression of Fc-γ Receptors on Monocytes in Patients With Nascent Metabolic Syndrome [J].
Devaraj, Sridevi ;
Chen, Xinpu ;
Adams-Huet, Beverley ;
Jialal, Ishwarlal .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2013, 98 (09) :E1510-E1515
[7]  
Dispinseri S, DATA ROBUST NEUTRALI
[8]   Antibodies and B cell memory in viral immunity [J].
Doerner, Thomas ;
Radbruch, Andreas .
IMMUNITY, 2007, 27 (03) :384-392
[9]   Immunogenicity, safety, and effectiveness of seasonal influenza vaccination in patients with diabetes mellitus: A systematic review [J].
Dos Santos, Gael ;
Tahrat, Halima ;
Bekkat-Berkani, Rafik .
HUMAN VACCINES & IMMUNOTHERAPEUTICS, 2018, 14 (08) :1853-1866
[10]   A case presentation for positive SARS-CoV-2 RNA recurrence in a patient with a history of type 2 diabetes that had recovered from severe COVID-19 [J].
Dou, Chengyun ;
Xie, Xia ;
Peng, Zhongtian ;
Tang, Haibo ;
Jiang, Zheng ;
Zhong, Zhefeng ;
Tang, Jian .
DIABETES RESEARCH AND CLINICAL PRACTICE, 2020, 166