Neutralizing Antibody Responses to Severe Acute Respiratory Syndrome Coronavirus 2 in Coronavirus Disease 2019 Inpatients and Convalescent Patients

Abstract

Background Coronavirus disease 2019 (COVID-19) is a pandemic with no specific antiviral treatments or vaccines. There is an urgent need for exploring the neutralizing antibodies from patients with different clinical characteristics. Methods A total of 117 blood samples were collected from 70 COVID-19 inpatients and convalescent patients. Antibodies were determined with a modified cytopathogenic neutralization assay (NA) based on live severe acute respiratory syndrome coronavirus 2 and enzyme-linked immunosorbent assay (ELISA). The dynamics of neutralizing antibody levels at different time points with different clinical characteristics were analyzed. Results The seropositivity rate reached up to 100.0% within 20 days since onset, and remained 100.0% till days 41–53. The total geometric mean titer was 1:163.7 (95% confidence interval [CI], 128.5–208.6) by NA and 1:12 441.7 (95% CI, 9754.5–15 869.2) by ELISA. The antibody level by NA and ELISA peaked on days 31–40 since onset, and then decreased slightly. In multivariate generalized estimating equation analysis, patients aged 31–45, 46–60, and 61–84 years had a higher neutralizing antibody level than those aged 16–30 years (β = 1.0470, P = .0125; β = 1.0613, P = .0307; β = 1.3713, P = .0020). Patients with a worse clinical classification had a higher neutralizing antibody titer (β = 0.4639, P = .0227). Conclusions The neutralizing antibodies were detected even at the early stage of disease, and a significant response was shown in convalescent patients.

Neutralizing antibodies from early cases of SARS-CoV-2 infection offer cross-protection against the SARS-CoV-2 D614G variant

“…Figure 1D and 1E, Supplementary figure 1). Notably, these antibodies were able to neutralize both SARS-CoV-2 D614 and G614 pseudoviruses at similar levels, despite having a significantly lower neutralization capacity at median 98 days pio in all COVID-19 patients ( Figure 1D and 1E Supplementary figure 2) (15,16). Of clinical importance, all the patients infected with either the D614 or G614 clade elicited a similar degree of neutralization against both D614 and G614 pseudoviruses ( Figure 1F), suggesting that the D614G mutation does not impact the neutralization capacity of the elicited antibodies.…”

Humoral immune responses and neutralizing antibodies against SARS-CoV-2; implications in pathogenesis and protective immunity

“…SARS-CoV and SARS-CoV-2 have a 80% homology and share approximately 75% of the spike glycoprotein sequence [ 7 , 33 ]. Although, few antibodies that exhibit cross-neutralizing activity between SARS-CoV and SARS-CoV-2 have been identified [ 34 ], the existence of potentially cross-reactive antibodies opens new avenues for the potential development of a pan-neutralizing vaccines against various coronaviruses [ 31 ].…”

“…Neutralizing antibodies are detected in approximately 40%–70% of infected individuals, depending on the criteria and the cohort studied. At least 30% of patients have no detectable antibody levels and less than 15% reach high titers of neutralization in vitro [ [34] , [35] , [36] , [37] ]. An association between neutralizing antibody titer and severity of COVID-19 disease has been observed and those who have mild symptoms or are asymptomatic are more reluctant to generate a neutralizing response [ 38 ].…”

Updated guidance on the management of COVID-19: from an American Thoracic Society/European Respiratory Society coordinated International Task Force (29 July 2020)

“…Data from a limited number of cohort studies of hospitalised patients with COVID-19 suggest that almost 100% of hospitalised patients will develop immunoglobulin (Ig)M and IgG antibodies by the tenth day of hospitalisation [48][49][50][51][52][53]. Several correlations have been observed: more severe disease is associated with higher antibody levels; more severe disease is associated with higher titres of neutralising antibodies and higher total antibody levels are associated with higher levels of neutralising antibodies.…”