Analysis of Neutralization Antibodies in Patients With Mild COVID-19 Infection After 100 Days Using Microneutralization Test

Min-Ju Ahn^1,2,3 , Dae Gwin Jeong^1,2,3 , Kyu-Sun Lee³ , Seungjun Lee⁴ , Byung-Han Ryu⁵ , Hye Ryun Yang⁶ , Sunjoo Kim^4,6,7

¹Infectious Disease Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon
²Bio-Analytical Science Division, University of Science and Technology, Daejeon
³Bionanotechnology Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon
⁴Department of Laboratory Medicine, Gyeongsang National University Changwon Hospital, Changwon
⁵Department of Infectious Diseases, Gyeongsang National University Changwon Hospital, Changwon
⁶Gyeongnam Center for Infectious Disease Control and Prevention, Changwon
⁷Gyeongsang Institute of Health Sciences, Gyeongsang National University College of Medicine, Jinju, Korea

Corresponding author : sjkim8239@hanmail.net

March 2022
The Annals of Clinical Microbiology 2022 25(1):29-33
Received Date: April 14, 2021
Revised Date: March 03, 2022
Accepted Date: March 07, 2022
DOI: 10.5145/ACM.2022.25.1.4
Citation

ABSTRACT

Neutralizing antibodies play a critical role in blocking viral infections and in viral clearance during acute infection. The microneutralization assay and enzyme-linked immunosorbent assay (ELISA) targeting the receptor binding domain were performed for 30 patients with mild coronavirus disease (COVID)-19 infections. The elapsed number of days between sample collection and diagnosis was 115 days, and real-time polymerase chain reaction (PCR) cycle threshold (Ct) values at diagnosis were recorded. Clinical characteristics and Ct values were compared between neutralization antibody-positive and -negative patients as measured by the microneutralization assay. Neutralization antibody-positive patients (n = 9) were likely to be older, have low Ct values, have more pneumonia during admission, and have a higher optical density in ELISA than the neutralization antibody-negative patients (n = 21). Elderly people seemed to have a higher viral load causing more pneumonia and to produce more neutralization antibodies. Neutralization antibodies persisted in only 30% of patients as detected by microneutralization test after 100 days of diagnosis.

Keywords

Antibody, COVID-19, Neutralization, SARS-CoV-2

Figures & Tables

 

Table 1. Clinical characteristics, differences in Ct values and ELISAOD between neutralizing antibody-positive and -negative patients measured by microneutralization

Characteristic	Neutralizing antibody				P-value
	Positive (n = 9) No. (%)	Negative (n = 21) No. (%)	Total (n = 30) No. (%)
Sex, male	5 (55.6)	8 (38.1)	13 (43.3)	0.630
Age (yr)*	53.4 ± 9.9	40.8 ± 14.4	44.6 ± 14.3	0.033
Presentation of COVID-19
NEWS score at admission†	1 [0–1.5]	0 [0–1.5]	1 [0–1.25]	0.504
Pneumonia	8 (88.9)	8 (38.1)	16 (53.3)	0.017
Oxygen support via nasal prong	1 (11.1)	0	1 (3.3)	0.300
Asymptomatic patients	0	3 (14.3)	3 (10.0)	0.530
Interval of diagnosis and sample collection(days)*	112.7 ± 15.9	116.4 ± 14.5	115.3 ± 14.8	0.525
Ct value†
E	19.3 [18.8–19.6]	27.4 [22.4–30.1]	23.2 [19.3–28.6]	0.005
RdRp	17.9 [16.9–20.0]	27.9 [23.5–32.0]	24.6 [17.9–29.8]	0.003
N	20.7 [19.4–22.2]	24.0 [19.6–30.5]	21.8 [19.6–24.0]	0.236
Neutralizing antibody reciprocal titer†	80 [80–160]	20 [10–40]	40 [20–80]
ELISA OD†	0.89 [0.63–0.92]	0.35 [0.26–0.45]	0.44 [0.28–0.67]	0.002
*mean ± SD; †median [IQR].
Abbreviations: Ct, cycle threshold; ELISA, enzyme-linked immunosorbent assay; OD, optical density; SD, standard deviation; COVID, coronavirus disease; arly warning score; IQR, interquartile range.