Post by Nadica (She/Her) on Jul 8, 2024 4:46:02 GMT
MENSA, a Media Enriched with Newly Synthesized Antibodies, to Identify SARS-CoV-2 Persistence and Latent Viral Reactivation in Long-COVID - Preprint posted July 7, 2024
Abstract
Post-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.
Competing Interest Statement
FEL is the founder of MicroB-plex, Inc. and serves on the scientific board of Be Biopharma, is a recipient of grants from the BMGF and Genentech, Inc., and has served as a consultant for Astra Zeneca. NSH and AMP were scientists at MicroB-plex, Inc., Atlanta, GA and JLD is a scientist at MicroB-plex, Inc., Atlanta, GA. IS has consulted for GSK, Pfizer, Kayverna, Johnson & Johnson, Celgene, Bristol Myer Squibb, and Visterra. FEL, DN, and IS are inventors of the patents concerning the plasma cell survival media related to this work (issued 9/21/21, US 11,124766 B2 PCT/US2016/036650; and issued 9/21/21, US 11,125757 B2). FEL & JLD are inventors of MENSA patent U.S. Patent No. 10,247,729. April 2, 2019. FEL, NSH, JLD, & IS are inventors of the MENSA PASC diagnostic provisional patent, March 28, 2024. All other authors have declared that no conflict of interest exists.
Funding Statement
This work was supported by National Institute of Allergy and Infectious Diseases, National Institutes of Health 3P01AI125180-05S1, R01AI121252, R01AI 172254, P01A1078907, U01AI045969, U19AI109962, U54CA260563, T32HL116271-07, and NIGMS 2T32GM095442, NIH Department of Health and Human Services/Public Health Services: 5T32AI74492-14.
Abstract
Post-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.
Competing Interest Statement
FEL is the founder of MicroB-plex, Inc. and serves on the scientific board of Be Biopharma, is a recipient of grants from the BMGF and Genentech, Inc., and has served as a consultant for Astra Zeneca. NSH and AMP were scientists at MicroB-plex, Inc., Atlanta, GA and JLD is a scientist at MicroB-plex, Inc., Atlanta, GA. IS has consulted for GSK, Pfizer, Kayverna, Johnson & Johnson, Celgene, Bristol Myer Squibb, and Visterra. FEL, DN, and IS are inventors of the patents concerning the plasma cell survival media related to this work (issued 9/21/21, US 11,124766 B2 PCT/US2016/036650; and issued 9/21/21, US 11,125757 B2). FEL & JLD are inventors of MENSA patent U.S. Patent No. 10,247,729. April 2, 2019. FEL, NSH, JLD, & IS are inventors of the MENSA PASC diagnostic provisional patent, March 28, 2024. All other authors have declared that no conflict of interest exists.
Funding Statement
This work was supported by National Institute of Allergy and Infectious Diseases, National Institutes of Health 3P01AI125180-05S1, R01AI121252, R01AI 172254, P01A1078907, U01AI045969, U19AI109962, U54CA260563, T32HL116271-07, and NIGMS 2T32GM095442, NIH Department of Health and Human Services/Public Health Services: 5T32AI74492-14.