Dynamics of neutralizing antibody responses in acute-phase COVID-19: A potential relationship between disease progression and rapid neutralizing antibody response

Abstract

Introduction Adaptive immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) dynamics remain largely unknown. The neutralizing antibody (NAb) levels in patients with coronavirus disease 2019 (COVID-19) are helpful for understanding the pathology. Patients and Methods Using SARS-CoV-2 pseudotyped virus, serum sample neutralization values in symptomatic COVID-19 patients were measured using the chemiluminescence reduction neutralization test (CRNT). At least two sequential serum samples collected during hospitalization were analyzed to assess NAbs neutralizing activity dynamics at different time points. Results Of the 11 patients, four (36.4%), six (54.5%), and one (9.1%) had moderate, severe, and critical disease, respectively. Fifty percent neutralization (N50%-CRNT) was observed upon admission in 90.9% (10/11); all patients acquired neutralizing activity 2–12 days after onset. In patients with moderate disease, neutralization was observed at earliest within two days after symptom onset. In patients with severe-to-critical disease, neutralization activity increased, plateauing 9–16 days after onset. Neutralization activity on admission was significantly higher in patients with moderate disease than in patients with severe-to-critical disease (relative % of infectivity, 6.4% vs. 41.1%; P=.0011). Conclusions Neutralization activity on admission inversely correlated with disease severity. The rapid NAb response may play a crucial role in preventing the progression of COVID-19.

Correlation of the commercial anti-SARS-CoV-2 receptor binding domain antibody test with the chemiluminescent reduction neutralizing test and possible detection of antibodies to emerging variants

“…The CRNT can assess the inhibitory effect of serum samples on viral attachment and entry into the target cells. As observed in our previous reports (1, 2), the inhibition of the infectivity of sera from symptomatic COVID-19 patients gradually increased during the follow-up period, suggesting that the CRNT reflects the status of immunity acquisition. Meanwhile, commercial antibody tests that do not specify functional antibodies are becoming available.…”

“…These samples were collected from confirmed COVID-19 patients (n = 74), confirmed non-COVID-19 individuals (n = 179), and unscreened individuals (suspected healthy individuals) (n = 229) ( Table 1 ). Because in our previous study, moderate and severe patients with COVID-19 showed > 50% inhibition (IC 50 ) in the CRNT after day 10 from disease onset (2), the period after day 10 from disease onset was considered as the convalescent phase. Neutralization activity against pseudotyped viruses and anti-RBD antibody levels were evaluated by the CRNT ( Figure 1A ) and quantified by the commercially available test ( Figure 1B ).…”