Delayed neutralizing antibody response in the acute phase correlates with severe progression of COVID-19

Hitoshi Kawasuji,Makito Kaneda,Yoshihiro Yamamoto,Koyomi Kawago,Hiroshi Yamada,Akitoshi Ueno,Ippei Sakamaki,Yasutaka Fukui,Yuki Miyajima,Yushi Murai,Miyuki Kimura,Yoshitomo Morinaga,Yusuke Takegoshi,Yoshihiro Yoshida,Kou Kimoto,Hideki Tani

doi:10.1038/s41598-021-96143-8

Hitoshi Kawasuji, Makito Kaneda + Show 14 more

Open Access

https://doi.org/10.1038/s41598-021-96143-8

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Abstract

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. 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. 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 = .011). 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.

Highlights

Adaptive immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) dynamics remain largely unknown
To circumvent the need for BSL-3 laboratories, we recently developed a fundamental neutralizing antibody (NAb) detection method for SARS-CoV-2 based on the chemiluminescence reduction neutralization test (CRNT) and VSV-based pseudotyped viruses with SARS-CoV-2 S (Sfullpv) or truncated S proteins (St19pv) to evaluate the expression and neutralization values of NAbs against SARS-CoV-26
At least two sequential serum samples collected on admission and during hospitalization from confirmed symptomatic COVID-19 patients with different disease severities were analyzed to assess the dynamics of the neutralizing activities of NAbs at different time points and determine the clinical significance of the measurement results using our fundamental NAbs detection method

Summary

Introduction

Adaptive immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) dynamics remain largely unknown. Recent evidence shows that recovered COVID-19 patients can generate antibodies, albeit at variable levels, that bind to various structural proteins of SARS-CoV-2 particles shortly after the onset of d isease[1,2,3] Among these virus-specific antibodies, only those capable of blocking SARS-CoV-2 spike (S) protein-mediated viral attachment and/or entry of host cells, called neutralizing antibodies (NAbs), play an important role in virus clearance and have been considered as key immune products in the protection against or treatment of viral diseases. At least two sequential serum samples collected on admission and during hospitalization from confirmed symptomatic COVID-19 patients with different disease severities were analyzed to assess the dynamics of the neutralizing activities of NAbs at different time points and determine the clinical significance of the measurement results using our fundamental NAbs detection method

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