Kinetics and Correlates of the Neutralizing Antibody Response to SARS-CoV-2

Abstract

A detailed understanding of antibody-based SARS-CoV-2 immunity has critical implications for overcoming the COVID-19 pandemic and for informing on vaccination strategies. In this study, we evaluated the dynamics of the SARS-CoV-2 antibody response in a cohort of 963 recovered individuals over a period of 10 months. Investigating a total of 2,146 samples, we detected an initial SARS-CoV-2 antibody response in 94.4% of individuals, with 82% and 79% exhibiting serum and IgG neutralization, respectively. Approximately 3% of recovered patients demonstrated exceptional SARS-CoV-2 neutralizing activity, de ning them as 'elite neutralizers'. These individuals also possessed effective cross-neutralizing IgG antibodies to SARS-CoV-1 without any known prior exposure to this virus. By applying multivariate statistical modeling, we found that sero-reactivity, age, time since disease onset, and fever are key factors predicting SARS-CoV-2 neutralizing activity in mild courses of COVID-19. Investigating longevity of the antibody response, we detected loss of anti-spike reactivity in 13% of individuals 10 months after infection. Moreover, neutralizing activity had an initial half-life of 6.7 weeks in serum versus 30.8 weeks in puri ed IgG samples indicating the presence of a more stable and long-term memory IgG B cell repertoire in the majority of individuals recovered from COVID-19. Our results demonstrate a broad spectrum of the initial SARS-CoV-2 neutralizing antibody response depending on clinical characteristics, with antibodies being maintained in the majority of individuals for the rst 10 months after mild course of COVID-19. Main COVID-19 is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which was rst identi ed in December 2019 1,2. Since then, the virus has rapidly spread across the globe and caused more than 90 million proven infections and over 2 million deaths. Disease severity ranges from asymptomatic infection to symptoms like cough, fever, muscle pain, and diarrhea to severe courses of infection including pneumonia with severe respiratory distress and a high risk of death 3-5. While the majority of infected individuals experience a mild course of disease, elderly or individuals with preexisting conditions are at higher risk for severe courses of COVID-19 6. In symptomatic non-hospitalized cases, the acute course of disease typically spans 7-14 days 7,8. However, a signi cant fraction of COVID-19 patients suffer long-lasting symptoms post recovery, so called 'post-COVID syndrome' 9-11 (Augustin et al., submitted). SARS-CoV-2 infects human cells by using the virus spike (S) protein 12 for targeting the angiotensin converting enzyme-2 (ACE-2) receptor 13. The S-protein carries dominant epitopes against which humoral B and T cell responses are generated upon natural infection and vaccination 14-18. Spike-speci c IgM, IgA, and IgG antibodies are detected early after infection 19,20 and IgG antibody levels and IgG memory B cells can persist post infection 21. Neutralizing antibodies (NAbs) ar...

SARS-CoV-2 Portrayed against HIV: Contrary Viral Strategies in Similar Disguise

“…The early anti-SARS-CoV-2 binding and nAb response is dominated by IgM, which wanes rapidly. IgA and IgG peak subsequently, and IgG-mediated neutralizing responses are most durable and persist over months, mirrored by neutralization half-lives of a few months in serum but up to >8 months in purified IgG samples [ 242 , 243 , 244 , 245 ]. The persisting Ab response can be attributed to a maturing humoral immunity driven by a sustained SARS-CoV-2 antigenic stimulation in the gut of COVID-19 patients [ 246 ].…”

Intranasal administration of a monoclonal neutralizing antibody protects mice against SARS-CoV-2 infection

“…As these results highlight DZIF-10c as a very potent S-binding antibody, we further characterized its neutralizing properties. The in vitro neutralizing activity of DZIF-10c was first evaluated against a panel of six pseudovirus variants (23,24). DZIF-10c demonstrated potent neutralizing activity against all SARS-CoV-2 S variants tested, including a variant carrying the D614G mutation, with an average IC 50 of 0.007 µg/ml (Fig.…”