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Dynamics of neutralizing antibody responses to SARS-CoV-2 in patients with COVID-19: an observational study.

ABSTRACT: Our understanding of the protective immunity, particularly the long-term dynamics of neutralizing antibody (NAbs) response to SARS-CoV-2, is currently limited. We enrolled a cohort of 545 COVID-19 patients from Hubei, China, who were followed up up to 7 months, and determined the dynamics of NAbs to SARS-CoV-2 by using a surrogate virus neutralization test (sVNT). In our validation study, sVNT IC₅₀ titers and the neutralization rate measured at a single dilution (1:20) were well correlated with FRNT titers (r = 0.85 and 0.84, respectively). The median time to seroconversion of NAbs was 5.5 days post onset of symptoms. The rate of positive sVNT was 52% in the first week, reached 100% in the third week, and remained above 97% till 6 months post onset. Quantitatively, NAbs peaked in the fourth week and only a quarter of patients had an estimated peak titer of >1000. NAbs declined with a half-time of 61 days (95% CI: 49-80 days) within the first two months, and the decay deaccelerated to a half-time of 104 days (95% CI: 86-130 days) afterward. The peak levels of NAbs were positively associated with severity of COVID-19 and age, while negatively associated with serum albumin levels. The observation that the low-moderate peak neutralizing activity and fast decay of NAbs in most naturally infected individuals called for caution in evaluating the feasibility of antibody-based therapy and vaccine durability. NAbs response positively correlated with disease severity, warning for the possibility of repeat infection in patients with mild COVID-19.

SUBMITTER: Xu X

PROVIDER: S-EPMC8129700 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (Covid-19), which is most frequently mild yet can be severe and life-threatening. Virus-neutralizing monoclonal antibodies are predicted to reduce viral load, ameliorate symptoms, and prevent hospitalization.MethodsIn this ongoing phase 2 trial involving outpatients with recently diagnosed mild or moderate Covid-19, we randomly assigned 452 patients to receive a single intravenous infusion of neutralizing antibody LY-CoV555 in one of three doses (700 mg, 2800 mg, or 7000 mg) or placebo and evaluated the quantitative virologic end points and clinical outcomes. The primary outcome was the change from baseline in the viral load at day 11. The results of a preplanned interim analysis as of September 5, 2020, are reported here.ResultsAt the time of the interim analysis, the observed mean decrease from baseline in the log viral load for the entire population was -3.81, for an elimination of more than 99.97% of viral RNA. For patients who received the 2800-mg dose of LY-CoV555, the difference from placebo in the decrease from baseline was -0.53 (95% confidence interval [CI], -0.98 to -0.08; P = 0.02), for a viral load that was lower by a factor of 3.4. Smaller differences from placebo in the change from baseline were observed among the patients who received the 700-mg dose (-0.20; 95% CI, -0.66 to 0.25; P = 0.38) or the 7000-mg dose (0.09; 95% CI, -0.37 to 0.55; P = 0.70). On days 2 to 6, the patients who received LY-CoV555 had a slightly lower severity of symptoms than those who received placebo. The percentage of patients who had a Covid-19-related hospitalization or visit to an emergency department was 1.6% in the LY-CoV555 group and 6.3% in the placebo group.ConclusionsIn this interim analysis of a phase 2 trial, one of three doses of neutralizing antibody LY-CoV555 appeared to accelerate the natural decline in viral load over time, whereas the other doses had not by day 11. (Funded by Eli Lilly; BLAZE-1 ClinicalTrials.gov number, NCT04427501.).

Project description:Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has swept the world and poses a significant global threat to lives and livelihoods, with 115 million confirmed cases and at least 2.5 million deaths from Coronavirus disease 2019 (COVID-19) in the first year of the pandemic. Developing tools to measure seroprevalence and understand protective immunity to SARS-CoV-2 is a priority. We aimed to develop a serological assay using plant-derived recombinant viral proteins, which represent important tools in less-resourced settings. Methods: We established an indirect ELISA using the S1 and receptor-binding domain (RBD) portions of the spike protein from SARS-CoV-2, expressed in Nicotiana benthamiana. We measured antibody responses in sera from South African patients (n = 77) who had tested positive by PCR for SARS-CoV-2. Samples were taken a median of 6 weeks after the diagnosis, and the majority of participants had mild and moderate COVID-19 disease. In addition, we tested the reactivity of pre-pandemic plasma (n = 58) and compared the performance of our in-house ELISA with a commercial assay. We also determined whether our assay could detect SARS-CoV-2-specific IgG and IgA in saliva. Results: We demonstrate that SARS-CoV-2-specific immunoglobulins are readily detectable using recombinant plant-derived viral proteins, in patients who tested positive for SARS-CoV-2 by PCR. Reactivity to S1 and RBD was detected in 51 (66%) and 48 (62%) of participants, respectively. Notably, we detected 100% of samples identified as having S1-specific antibodies by a validated, high sensitivity commercial ELISA, and optical density (OD) values were strongly and significantly correlated between the two assays. For the pre-pandemic plasma, 1/58 (1.7%) of samples were positive, indicating a high specificity for SARS-CoV-2 in our ELISA. SARS-CoV-2-specific IgG correlated significantly with IgA and IgM responses. Endpoint titers of S1- and RBD-specific immunoglobulins ranged from 1:50 to 1:3,200. S1-specific IgG and IgA were found in saliva samples from convalescent volunteers. Conclusion: We demonstrate that recombinant SARS-CoV-2 proteins produced in plants enable robust detection of SARS-CoV-2 humoral responses. This assay can be used for seroepidemiological studies and to measure the strength and durability of antibody responses to SARS-CoV-2 in infected patients in our setting.

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Dynamics of neutralizing antibody responses to SARS-CoV-2 in patients with COVID-19: an observational study.

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