MENSA, a Media Enriched with Newly Synthesized Antibodies, to Identify SARS-CoV-2 Persistence and Latent Viral Reactivation in Long-COVID

Author:

Haddad Natalie S.ORCID,Morrison-Porter Andrea,Quehl Hannah,Capric Violeta,Lamothe Pedro A.,Anam Fabliha,Runnstrom Martin C.,Truong Alex D.,Dixit Adviteeya N.,Woodruff Matthew C.,Chen Anting,Park Jiwon,Nguyen Doan C.,Hentenaar Ian,Kim Caroline Y.,Kyu Shuya,Stewart Brandon,Wagman Elizabeth,Geoffroy Hannah,Sanz Daniel,Cashman Kevin S.,Ramonell Richard P.,Cabrera-Mora Monica,Alter David N.,Roback John D.,Horwath Michael C.,O’Keefe James B.,Dretler Alexandra W.,Gripaldo Ria,Yeligar Samantha M.,Natoli Ted,Betin Viktoria,Patel Rahulkumar,Vela Kennedy,Hernandez Mindy Rodriguez,Usman Sabeena,Varghese John,Jalal Anum,Lee SaeyunORCID,Le Sang N.,Toby Amoss R.,Daiss John L.ORCID,Sanz IgnacioORCID,Lee F. Eun-Hyung

Abstract

ABSTRACTPost-acute sequelae of SARS-CoV-2 (SARS2) infection (PASC) is a heterogeneous condition, but the main viral drivers are unknown. Here, we use MENSA, Media Enriched with Newly Synthesized Antibodies, secreted exclusively from circulating human plasmablasts, to provide an immune snapshot that defines the underlying viral triggers. We provide proof-of-concept testing that the MENSA technology can capture the new host immune response to accurately diagnose acute primary and breakthrough infections when known SARS2 virus or proteins are present. It is also positive after vaccination when spike proteins elicit an acute immune response. Applying the same principles for long-COVID patients, MENSA is positive for SARS2 in 40% of PASC vs none of the COVID recovered (CR) patients without any sequelae demonstrating ongoing SARS2 viral inflammation only in PASC. Additionally, in PASC patients, MENSAs are also positive for Epstein-Barr Virus (EBV) in 37%, Human Cytomegalovirus (CMV) in 23%, and herpes simplex virus 2 (HSV2) in 15% compared to 17%, 4%, and 4% in CR controls respectively. Combined, a total of 60% of PASC patients have a positive MENSA for SARS2, EBV, CMV, and/or HSV2. MENSA offers a unique antibody snapshot to reveal the underlying viral drivers in long-COVID thus demonstrating the persistence of SARS2 and reactivation of viral herpes in 60% of PASC patients.Graphical abstract

Publisher

Cold Spring Harbor Laboratory

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