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Evidence for sustained mucosal and systemic antibody responses to SARS-CoV-2 antigens in COVID-19 patients
Baweleta Isho; Kento T Abe; Michelle Zuo; Alainna J Jamal; Bhavisha Rathod; Jenny H Wang; Zhijie Li; Gary Chao; Olga L Rojas; Yeo Myong Bang; Annie Pu; Natasha Christie-Holmes; Christian Gervais; Derek Ceccarelli; Payman Samavarchi-Tehrani; Furkan Guvenc; Patrick Budylowski; Angel Li; Aimee Paterson; Yue Feng Yun; Lina M Marin; Lauren Caldwell; Jeffrey L Wrana; Karen Colwill; Frank Sicheri; Samira Mubareka; Scott D Gray-Owen; Steven J Drews; Walter L Siqueira; Miriam Barrios-Rodiles; Mario Ostrowski; James M Rini; Yves Durocher; Allison J McGeer; Jennifer L Gommerman; Anne-Claude Gingras.
  • Baweleta Isho; Department of Immunology, University of Toronto, Toronto, Ontario
  • Kento T Abe; Lunenfeld-Tanenbaum Research Institute at Mount Sinai Hospital, Sinai Health System, Toronto, Ontario; Department of Molecular Genetics, University of Toronto,
  • Michelle Zuo; Department of Immunology, University of Toronto, Toronto, Ontario
  • Alainna J Jamal; Department of Microbiology, at Mount Sinai Hospital, Sinai Health System, Toronto, ON, Canada; Institute of Health Policy, Management and Evaluation, University
  • Bhavisha Rathod; Lunenfeld-Tanenbaum Research Institute at Mount Sinai Hospital, Sinai Health System, Toronto, Ontario
  • Jenny H Wang; Lunenfeld-Tanenbaum Research Institute at Mount Sinai Hospital, Sinai Health System, Toronto, Ontario
  • Zhijie Li; Department of Molecular Genetics, University of Toronto, Toronto, Ontario
  • Gary Chao; Department of Immunology, University of Toronto, Toronto, Ontario
  • Olga L Rojas; Department of Immunology, University of Toronto, Toronto, Ontario
  • Yeo Myong Bang; Department of Immunology, University of Toronto, Toronto, Ontario
  • Annie Pu; Department of Immunology, University of Toronto, Toronto, Ontario
  • Natasha Christie-Holmes; Combined Containment Level 3 Unit, University of Toronto, Toronto, Ontario
  • Christian Gervais; Mammalian Cell Expression, Human Health Therapeutics Research Centre, National Research Council Canada, Montreal, Quebec
  • Derek Ceccarelli; Lunenfeld-Tanenbaum Research Institute at Mount Sinai Hospital, Sinai Health System, Toronto, Ontario
  • Payman Samavarchi-Tehrani; Lunenfeld-Tanenbaum Research Institute at Mount Sinai Hospital, Sinai Health System, Toronto, Ontario
  • Furkan Guvenc; Department of Molecular Genetics, University of Toronto, Toronto, Ontario
  • Patrick Budylowski; Institute of Medical Science, University of Toronto; Combined Containment Level 3 Unit, University of Toronto, Toronto, Ontario
  • Angel Li; Department of Microbiology, at Mount Sinai Hospital, Sinai Health System, Toronto, ON, Canada
  • Aimee Paterson; Department of Microbiology, at Mount Sinai Hospital, Sinai Health System, Toronto, ON, Canada
  • Yue Feng Yun; Department of Immunology, University of Toronto, Toronto, Ontario
  • Lina M Marin; College of Dentistry, University of Saskatchewan, Saskatoon, Saskatchewan
  • Lauren Caldwell; Lunenfeld-Tanenbaum Research Institute at Mount Sinai Hospital, Sinai Health System, Toronto, Ontario
  • Jeffrey L Wrana; Lunenfeld-Tanenbaum Research Institute at Mount Sinai Hospital, Sinai Health System, Toronto, Ontario; Department of Molecular Genetics, University of Toronto,
  • Karen Colwill; Lunenfeld-Tanenbaum Research Institute at Mount Sinai Hospital, Sinai Health System, Toronto, Ontario
  • Frank Sicheri; Lunenfeld-Tanenbaum Research Institute at Mount Sinai Hospital, Sinai Health System, Toronto, Ontario; Department of Molecular Genetics, University of Toronto,
  • Samira Mubareka; Sunnybrook Research Institute, Toronto, ON, Canada and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON
  • Scott D Gray-Owen; Department of Molecular Genetics, University of Toronto, Toronto, Ontario; Combined Containment Level 3 Unit, University of Toronto, Toronto, Ontario
  • Steven J Drews; Canadian Blood Services, Edmonton, AB & Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB, Canada
  • Walter L Siqueira; College of Dentistry, University of Saskatchewan, Saskatoon, Saskatchewan
  • Miriam Barrios-Rodiles; Lunenfeld-Tanenbaum Research Institute at Mount Sinai Hospital, Sinai Health System, Toronto, Ontario
  • Mario Ostrowski; St. Michaels Hospital, Toronto, Ontario, Li Ka Shing Knowledge Institute; Department of Immunology, University of Toronto, Toronto, Ontario
  • James M Rini; Department of Molecular Genetics, University of Toronto, Toronto, Ontario; Department of Biochemistry, University of Toronto, Toronto, ON, Canada
  • Yves Durocher; Mammalian Cell Expression, Human Health Therapeutics Research Centre, National Research Council Canada, Montreal, Quebec
  • Allison J McGeer; Lunenfeld-Tanenbaum Research Institute and Department of Microbiology at Mount Sinai Hospital, Sinai Health System; Institute of Health Policy, Management and E
  • Jennifer L Gommerman; Department of Immunology, University of Toronto, Toronto, Ontario
  • Anne-Claude Gingras; Lunenfeld-Tanenbaum Research Institute at Mount Sinai Hospital, Sinai Health System; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canad
Preprint En | PREPRINT-MEDRXIV | ID: ppmedrxiv-20166553
While the antibody response to SARS-CoV-2 has been extensively studied in blood, relatively little is known about the mucosal immune response and its relationship to systemic antibody levels. Since SARS-CoV-2 initially replicates in the upper airway, the antibody response in the oral cavity is likely an important parameter that influences the course of infection, but how it correlates to the antibody response in serum is not known. Here, we profile by enzyme linked immunosorbent assays (ELISAs) IgG, IgA and IgM responses to the SARS-CoV-2 spike protein (full length trimer) and its receptor binding domain (RBD) in serum (n=496) and saliva (n=90) of acute and convalescent patients with laboratory-diagnosed COVID-19 ranging from 3-115 days post-symptom onset (PSO), compared to negative controls. Anti-CoV-2 antibody responses were readily detected in serum and saliva, with peak IgG levels attained by 16-30 days PSO. Whereas anti-CoV-2 IgA and IgM antibodies rapidly decayed, IgG antibodies remained relatively stable up to 105 days PSO in both biofluids. In a surrogate neutralization ELISA (snELISA), neutralization activity peaks by 31-45 days PSO and slowly declines, though a clear drop is detected at the last blood draw (105-115 days PSO). Lastly, IgG, IgM and to a lesser extent IgA responses to spike and RBD in the serum positively correlated with matched saliva samples. This study confirms that systemic and mucosal humoral IgG antibodies are maintained in the majority of COVID-19 patients for at least 3 months PSO. Based on their correlation with each other, IgG responses in saliva may serve as a surrogate measure of systemic immunity. One Sentence SummaryIn this manuscript, we report evidence for sustained SARS-CoV-2-specific IgG and transient IgA and IgM responses both at the site of infection (mucosae) and systemically in COVID-19 patients over 3 months and suggest that saliva could be used as an alternative biofluid for monitoring IgG to SARS-CoV-2 spike and RBD antigens.

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