Circulating IgG and Vasopressin Levels in Mild-to-Moderate SARS-CoV-2 Infection Versus After Vaccination
Authors: Uyehara Catherine , Murata Lee-Ann , Kurata Wendy , Reichert-Scrivner Susan , Paguirigan Carmen , Hernandez Claudia , Kelly Gillian , Watase Colby , Angelo Jake , Barranco-Trabi Javier , Thompson Kristina , Ngauy Viseth 
Published: May 2023

Vasopressin (VP) has been shown to enhance SARS-CoV-2 infectivity by enabling virus entry into cells via VP receptor 1B-mediated endocytosis after forming a complex with SARS-CoV-2 spike protein and angiotensin converting enzyme II (ACE2). While elevated VP circulating levels in response to hypoxemic shock or osmotic dysregulation in severe COVID-19 is expected, altered VP levels associated with the early immunological response to mild cases of COVID-19, may be more subtle. We hypothesized that if circulating VP is involved in facilitating viral infection, changes in VP levels may occur in the absence of changes in osmolality or cardiovascular decompensation. We also postulated that there may be a difference in immunological responses in natural infection vs vaccine-induced immunity. Immune responses of asymptomatic to moderately symptomatic non-hospitalized individuals (n=63) diagnosed with SARS-CoV-2 infection by PCR test were followed up to a month from onset of infection and compared to that of matched controls (n=130). The responses from those never vaccinated (n=67) were compared against those who received 2 doses of the Pfizer COVID-19 vaccine (n=103) and those who received a 3rd booster dose of vaccine (n=23). Blood specimens were analyzed for quantitative measurement of IgG targeted to the SARS-Cov-2 spike protein (Epitope Diagnostics, San Diego, CA) and circulating AVP (by radioimmunoassay). Elevated IgG against spike protein was evident at 14 and 28 days from infection. IgG levels in naturally infected individuals (87±14 U/ml) were surpassed by levels achieved in 2 dose vaccinated uninfected individuals (505±82 U/ml) and those with vaccine breakthrough infections (920±160 U/ml). Those with a third boosted vaccine dose had 4x higher IgG levels (2411±457 U/ml) compared to 2 dose vaccination. Vaccine breakthrough infection in the boosted cohort saw a decrease in IgG levels (568±157 U/ml) three days after infection with a recovery of increased IgG production to (1189±302 U/ml) by day 28. VP levels in the naturally infected unvaccinated cohort (4.4±0.6 μU/ml) and vaccine breakthrough infection cohort (3.8±0.4 μU/ml) were higher than the uninfected vaccinated cohort (2.3 ± 0.2 μU/ml) without altered osmotic regulation. Results show exposure to SARS-CoV-2 spike protein increases immune IgG stimulation in a dose dependent manner. Enhanced VP response related to SARS-CoV-2 infection is consistent with a putative VP role in virus infectivity independent of a physiological role of osmotic regulation in non-severe cases of COVID-19. The views expressed are those of the authors and do not necessarily reflect the official policy or position of the Department of the Army, Department of Navy, Department of Defense, or the U.S. Government. This project was supported by the Joint Program Executive Office (JPEO-EB) W911QY-253 20-9-0004 (2020 OTA), and the Office of the Assistant Secretary of Defense for Health Affairs. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.