Mild SARS-CoV-2 Illness Is Not Associated with Reinfections and Provides Persistent Spike, Nucleocapsid, and Virus-Neutralizing Antibodies

• Published in: Microbiology spectrum Vol. 9; no. 2; p. e0008721
• Main Authors: Schuler, Charles F., Gherasim, Carmen, O’Shea, Kelly, Manthei, David M., Chen, Jesse, Zettel, Cristyn, Troost, Jonathan P., Kennedy, Andrew A., Tai, Andrew W., Giacherio, Donald A., Valdez, Riccardo, Baldwin, James L., Baker, James R.
• Format: Journal Article
• Language: English
• Published: 1752 N St., N.W., Washington, DC American Society for Microbiology 01.10.2021
• Subjects: antibody; Clinical Microbiology; COVID-19; nucleocapsid; Research Article; SARS-CoV-2; serology; spike; COVID-19; nucleocapsid; pseudoviral neutralization; SARS-CoV-2; vaccine; viral neutralization; antibody; serology; immunoserology; persistence; immunity; spike
• ISSN: 2165-0497; 2165-0497
• DOI: 10.1128/Spectrum.00087-21

This article demonstrates that people who have mild COVID-19 illnesses and produce antibodies are protected from reinfection for up to 6 months afterward. The antibodies that people produce in this situation are stable for up to 6 months as well. Uncertainty exists whether mild COVID-19 confers immunity to reinfection. Questions also remain regarding the persistence of antibodies against SARS-CoV-2 after mild infection. We prospectively followed at-risk individuals with and without SARS-CoV-2 for reinfection and monitored the spike and nucleocapsid antibodies. This prospective cohort study was conducted over two visits, 3 to 6 months apart, between May 2020 and February 2021. Adults with and without COVID-19, verified by FDA EUA-approved SARS-CoV-2 RT-PCR assays, were screened for spike and nucleocapsid antibody responses using FDA EUA-approved immunoassays and for pseudoviral neutralization activity. The subjects were monitored for symptoms, exposure to COVID-19, COVID-19 testing, seroconversion, reinfection, and vaccination. A total of 653 subjects enrolled; 129 (20%) had a history of COVID-19 verified by RT-PCR at enrollment. Most had mild disease, with only three requiring hospitalization. No initially seropositive subjects experienced a subsequent COVID-19 infection during the follow-up versus 15 infections among initially seronegative subjects (infection rates of 0.00 versus 2.05 per 10,000 days at risk [ P  = 0.0485]). In all, 90% of SARS-CoV-2-positive subjects produced spike and nucleocapsid responses, and all but one of these had persistent antibody levels at follow-up. Pseudoviral neutralization activity was widespread among participants, did not decrease over time, and correlated with clinical antibody assays. Reinfection with SARS-CoV-2 was not observed among individuals with mild clinical COVID-19, while infections continued in a group without known prior infection. Spike and nucleocapsid COVID-19 antibodies were associated with almost all infections and persisted at stable levels for the study duration. IMPORTANCE This article demonstrates that people who have mild COVID-19 illnesses and produce antibodies are protected from reinfection for up to 6 months afterward. The antibodies that people produce in this situation are stable for up to 6 months as well. Clinical antibody assays correlate well with evidence of antibody-related viral neutralization activity.