Neutralizing Antibody Production in Asymptomatic and Mild COVID-19 Patients, in Comparison with Pneumonic COVID-19 Patients

Ko, Jae-Hoon; Joo, Eun-Jeong; Park, Su‐Jin; Baek, Jin Yang; Kim, Won Duk; Jee, Jaehwan; Kim, Chul-Joong; Jeong, Cheol‐Ho; Kim, Yae-Jean; Shon, Hye Jin; Kang, Eun‐Suk; Choi, Young Ki; Peck, Kyong Ran

doi:10.3390/jcm9072268

Cited by 118 publications

(134 citation statements)

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“…suggesting either that they had not been produced or that they had already declined. Accordingly, Ko et al (2020) reported that most asymptomatic and mild COVID-19 patients produced NAbs, although the titers were lower than severe disease patients.…”

Section: Discussionmentioning

confidence: 99%

Anti-spike, Anti-nucleocapsid and Neutralizing Antibodies in SARS-CoV-2 Inpatients and Asymptomatic Individuals

et al. 2020

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A better understanding of the anti-SARS-CoV-2 immune response is necessary to finely evaluate commercial serological assays but also to predict protection against reinfection and to help the development of vaccines. For this reason, we monitored the anti-SARS-CoV-2 antibody response in infected patients. In order to assess the time of seroconversion, we used 151 samples from 30 COVID-19 inpatients and monitored the detection kinetics of anti-S1, anti-S2, anti-RBD and anti-N antibodies with inhouse ELISAs. We observed that specific antibodies were detectable in all inpatients 2 weeks post-symptom onset and that the detection of the SARS-CoV-2 Nucleocapsid and RBD was more sensitive than the detection of the S1 or S2 subunits. Using retroviral particles pseudotyped with the spike of the SARS-CoV-2, we also monitored the presence of neutralizing antibodies in these samples as well as 25 samples from asymptomatic individuals that were shown SARS-CoV-2 seropositive using commercial serological tests. Neutralizing antibodies reached a plateau 2 weeks post-symptom onset and then declined in the majority of inpatients but they were undetectable in 56% of asymptomatic patients. Our results indicate that the SARS-CoV-2 does not induce a prolonged neutralizing antibody response. They also suggest that induction of neutralizing antibodies is not the only strategy to adopt for the development of a vaccine. Finally, they imply that anti-SARS-CoV-2 neutralizing antibodies should be titrated to optimize convalescent plasma therapy.

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Section: Discussionmentioning

confidence: 99%

Anti-spike, Anti-nucleocapsid and Neutralizing Antibodies in SARS-CoV-2 Inpatients and Asymptomatic Individuals

et al. 2020

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“…For screening and confirmation of anti-SARS-CoV-2-binding antibody, we used a two-step protocol that included the FIA IgG kit and two ELISA kits for total and IgG antibody. In a previous study, the FIA IgG kit showed considerable sensitivity (98.8%) even in asymptomatic COVID-19 patients (Ko et al, 2020). The sensitivity of the FIA IgG kit was similar to or higher than that of ELISA kits (98.2% for total antibody and 94.4% for IgG), while ELISA kits were more specific (100% for total antibody and 99.6% for IgG) than the FIA IgG kit (94.1%).…”

Section: Discussionmentioning

confidence: 71%

“…To screen for the production of anti-SARS-CoV-2-binding antibodies among HCWs, we used a fluorescence immunoassay (FIA) kit (AFIAS COVID-19 Ab assay, Boditech Med Inc., Chuncheon, South Korea). In a previous study, FIA immunoglobulin G (IgG) showed considerable sensitivity (98.8%) for a range of conditions, including convalescent sera of asymptomatic patients to severe laboratory-confirmed COVID-19 patients (Ko et al, 2020). In an upcoming study using 110 RT-PCR-positive and 119 control samples, the sensitivity and specificity were 99.1 and 94.1%, respectively (data unpublished).…”

Section: Screening Strategymentioning

confidence: 93%

“…To evaluate the neutralization activity of the collected specimens, the MN assay against SARS-CoV-2 (Korean isolate; NMC-nCoV02) was performed in duplicate using 96-well tissue culture microplates (Greiner Bio-One, Kremsmünster, Austria) in a biosafety level 3 facility (Ko et al, 2020). We performed twofold serial dilution of inactivated patient serum starting at a dilution of 1:10 using Dulbecco modified Eagle medium (DMEM), incubated solutions with virus samples of 100 tissue culture infective dose 50 (TCID50) for 1 h at 37 • C, and then infected Vero cells with the cultures.…”

Section: Serum Neutralization Test (Microneutralization Assay)mentioning

confidence: 99%

“…However, asymptomatic or subclinical SARS-CoV-2 infections, which are thought to represent a large proportion of infections, could be missed by symptom-based RT-PCR screening strategies (Rivett et al, 2020). Recent evidence showed that asymptomatic and subclinical COVID-19 patients produced detectable amounts of anti-SARS-CoV-2 antibodies, suggesting that subclinical infection could be screened by serologic tests (Ko et al, 2020). To evaluate the risk of undetected SARS-CoV-2 transmission among HCWs caring for COVID-19 patients, we conducted a multicenter seroprevalence study after the first COVID-19 outbreak surge in the Republic of Korea.…”

Section: Introductionmentioning

confidence: 99%

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Serologic Evaluation of Healthcare Workers Caring for COVID-19 Patients in the Republic of Korea

Lee

Kim

et al. 2020

Front. Microbiol.

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The safety of healthcare workers (HCWs) against severe acute respiratory syndrome virus 2 (SARS-CoV-2) transmission is an important aspect of managing the coronavirus disease 2019 (COVID-19) pandemic. In the South Korea, highly stringent infection prevention and control (IPC) guidelines are implemented, and reports of healthcare-associated SARS-CoV-2 transmission among HCWs are limited. However, subclinical infections may have been missed by the current symptom-based screening strategy. To evaluate the risk of undetected SARS-CoV-2 transmissions from COVID-19 patients to HCWs, we conducted a multicenter seroprevalence study after the first surge of the COVID-19 outbreak. A total of 432 HCWs were evaluated, comprising 309 HCWs designated to laboratory-confirmed COVID-19 patient care and 123 non-designated HCWs. Designated HCWs wore personal protective equipment including an N95 respirator, eye protection, hooded overalls, shoe covers, and inner and outer gloves. Use of a powered air-purifying respirator was recommended for aerosol-generating procedures or long-duration care activities. A high-sensitivity (99.1%) fluorescence immunoassay immunoglobulin G (IgG) kit was used as the initial screening test, and two enzyme-linked immunosorbent assay kits for total and IgG antibodies were used to confirm the test results. A microneutralization test was additionally performed to evaluate the neutralizing activity of positive specimens. Among the evaluated HCWs, none of the non-designated HCWs had a positive result, while one of the HCWs designated for COVID-19 patient care (1/309, 0.3%) was seropositive for SARS-CoV-2 with confirmed neutralizing activity (1:40). This finding suggests that subclinical seroconversion may occur among HCWs caring for COVID-19 patients, although the risk is low under strict IPC guidance.

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Humoral response to SARS‐CoV‐2 and seasonal coronaviruses in COVID‐19 patients

Adams

Andrée

Rabl

et al. 2021

Journal of Medical Virology

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We used enzyme-linked immunoassay methods to measure the prevalence and the levels of antibody responses to the nucleocapsid (N) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and four seasonal human coronaviruses (HCoV-OC43, HCoV-HKU1, HCoV 229E, and HCoV-NL63) in a cohort of 115 convalescent plasma donors infected with SARS-CoV-2 (1-61 days after symptom onset) compared to antibody levels in 114 individuals with no evidence of a recent infection with SARS-CoV-2. In the humoral response to the four seasonal coronaviruses, only HCoV-HKU1-and HCoV-229E-assays showed slightly elevated antibody levels in the COVID group compared to the control group. While in the COVID-group the levels of SARS-CoV-2 antibodies correlated significantly with disease severity, no association was found in the levels of antibodies against the seasonal coronaviruses. The most striking result in both groups was that the levels of antibodies against all tested coronaviruses, including the new SARS-CoV-2 showed a highly significant correlation with each other. There seems to be an individual predisposition to a weaker or stronger humoral immune response against all known seasonal human coronaviruses including the new SARS-CoV-2, which could lead to a definition of low and high responders against human coronaviruses with potential impact on the assessment of postinfection antibody levels and protection.

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Neutralizing Antibody Production in Asymptomatic and Mild COVID-19 Patients, in Comparison with Pneumonic COVID-19 Patients

Cited by 118 publications

References 35 publications

Anti-spike, Anti-nucleocapsid and Neutralizing Antibodies in SARS-CoV-2 Inpatients and Asymptomatic Individuals

Anti-spike, Anti-nucleocapsid and Neutralizing Antibodies in SARS-CoV-2 Inpatients and Asymptomatic Individuals

Serologic Evaluation of Healthcare Workers Caring for COVID-19 Patients in the Republic of Korea

Humoral response to SARS‐CoV‐2 and seasonal coronaviruses in COVID‐19 patients

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