scholarly journals Magnitude and Kinetics of Anti–Severe Acute Respiratory Syndrome Coronavirus 2 Antibody Responses and Their Relationship to Disease Severity

Author(s):  
Kara L Lynch ◽  
Jeffrey D Whitman ◽  
Noreen P Lacanienta ◽  
Erica W Beckerdite ◽  
Shannon A Kastner ◽  
...  

Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can be detected indirectly by measuring the host immune response. For some viruses, antibody concentrations correlate with host protection and viral neutralization, but in rare cases, antiviral antibodies can promote disease progression. Elucidation of the kinetics and magnitude of the SARS-CoV-2 antibody response is essential to understand the pathogenesis of coronavirus disease 2019 (COVID-19) and identify potential therapeutic targets. Methods Sera (n = 533) from patients with real-time polymerase chain reaction–confirmed COVID-19 (n = 94 with acute infections and n = 59 convalescent patients) were tested using a high-throughput quantitative immunoglobulin M (IgM) and immunoglobulin G (IgG) assay that detects antibodies to the spike protein receptor binding domain and nucleocapsid protein. Individual and serial samples covered the time of initial diagnosis, during the disease course, and following recovery. We evaluated antibody kinetics and correlation between magnitude of the response and disease severity. Results Patterns of SARS-CoV-2 antibody production varied considerably. Among 52 patients with 3 or more serial specimens, 44 (84.6%) and 42 (80.8%) had observed IgM and IgG seroconversion at a median of 8 and 10 days, respectively. Compared to those with milder disease, peak measurements were significantly higher for patients admitted to the intensive care unit for all time intervals between 6 and 20 days for IgM, and all intervals after 5 days for IgG. Conclusions High-sensitivity assays with a robust dynamic range provide a comprehensive picture of host antibody response to SARS-CoV-2. IgM and IgG responses were significantly higher in patients with severe than mild disease. These differences may affect strategies for seroprevalence studies, therapeutics, and vaccine development.

Author(s):  
Kara L Lynch ◽  
Jeffrey D Whitman ◽  
Noreen P Lacanienta ◽  
Erica W Beckerdite ◽  
Shannon A Kastner ◽  
...  

AbstractBackgroundSARS-CoV-2 infection can be detected indirectly by measuring the host immune response. Anti-viral antibody concentrations generally correlate with host protection and viral neutralization, but in rare cases, antibodies can promote disease progression. Elucidation of the kinetics and magnitude of the SARS-CoV-2 antibody response is essential to understand the pathogenesis of COVID-19 and identify potential therapeutic targets.MethodsSera (n=533) from patients with RT-PCR confirmed COVID-19 (n=153) were tested using a high-throughput quantitative IgM and IgG assay that detects antibodies to the spike protein receptor binding domain and nucleocapsid protein. Individual and serial samples covered the time of initial diagnosis, during the disease course, and following recovery. We evaluated antibody kinetics and correlation between magnitude of the response and disease severity.ResultsPatterns of SARS-CoV-2 antibody production varied considerably. Among 52 patients with 3 or more serial specimens, 44 (84.6%) and 42 (80.8%) had observed IgM and IgG seroconversion at a median of 8 and 10 days, respectively. Compared to those with milder disease, peak measurements were significantly higher for patients admitted to the intensive care unit for all time intervals between 6 and 20 days for IgM, and all intervals after 5 days for IgG.ConclusionsHigh sensitivity assays with a robust dynamic range provide a comprehensive picture of host antibody response to SARS-CoV-2. IgM and IgG responses were significantly higher in patients with severe than mild disease. These differences may affect strategies for seroprevalence studies, therapeutics and vaccine development.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Chandima Jeewandara ◽  
Deshni Jayathilaka ◽  
Laksiri Gomes ◽  
Ananda Wijewickrama ◽  
Eranga Narangoda ◽  
...  

AbstractIn order to support vaccine development, and to aid convalescent plasma therapy, it would be important to understand the kinetics, timing and persistence of SARS-CoV-2 neutralizing antibodies (NAbs), and their association with clinical disease severity. Therefore, we used a surrogate viral neutralization test to evaluate their levels in patients with varying severity of illness, in those with prolonged shedding and those with mild/asymptomatic illness at various time points. Patients with severe or moderate COVID-19 illness had earlier appearance of NAbs at higher levels compared to those with mild or asymptomatic illness. Furthermore, those who had prolonged shedding of the virus, had NAbs appearing faster and at higher levels than those who cleared the virus earlier. During the first week of illness the NAb levels of those with mild illness was significantly less (p = 0.01), compared to those with moderate and severe illness. At the end of 4 weeks (28 days), although 89% had NAbs, 38/76 (50%) in those with > 90 days had a negative result for the presence of NAbs. The Ab levels significantly declined during convalescence (> 90 days since onset of illness), compared to 4 to 8 weeks since onset of illness. Our data show that high levels of NAbs during early illness associated with clinical disease severity and that these antibodies declined in 50% of individuals after 3 months since onset of illness.


2020 ◽  
Author(s):  
Chandima Jeewandara ◽  
Deshni Jayathilaka ◽  
Laksiri Gomes ◽  
Ananda Wijewickrama ◽  
Eranga Narangoda ◽  
...  

Abstract In order to support vaccine development, and to aid convalescent plasma therapy, it would be important to understand the kinetics, timing and persistence of SARS-CoV2 neutralizing antibodies (NAbs), and their association with clinical disease severity. Therefore, we used a surrogate viral neutralization test to evaluate their levels in patients with varying severity of illness, in those with prolonged shedding and those with mild/asymptomatic illness at various time points.Patients with severe or moderate COVID-19 illness had earlier appearance of NAbs at higher levels compared to those with mild or asymptomatic illness. Furthermore, those who had prolonged shedding of the virus, had NAbs appearing faster and at higher levels than those who cleared the virus earlier. During the first week of illness the NAb levels of those with mild illness was significantly less (p=0.01), compared to those with moderate and severe illness. At the end of 4 weeks (28 days), although 89% had Nabs, 38/76 (50%) in those with >90 days had a negative result for the presence of NAbs. The Ab levels significantly declined during convalescence (>90 days since onset of illness), compared to 4 to 8 weeks since onset of illness. Our data show that high levels of NAbs during early illness associated with clinical disease severity and that these antibodies declined in 50% of individuals after 3 months since onset of illness.


2020 ◽  
Vol 223 (1) ◽  
pp. 56-61 ◽  
Author(s):  
Lisa Henss ◽  
Tatjana Scholz ◽  
Christine von Rhein ◽  
Imke Wieters ◽  
Frauke Borgans ◽  
...  

Abstract Background The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has caused a pandemic with tens of millions of cases and hundreds of thousands of deaths. The infection causes coronavirus disease 2019 (COVID-19), a disease of the respiratory system of divergent severity. In the current study, humoral immune responses were characterized in a cohort of 143 patients with COVID-19 from the University Hospital Frankfurt am Main, Germany. Methods SARS-CoV-2-specific–antibodies were detected by enzyme-linked immunosorbent assay (ELISA). SARS-CoV-2 and human coronavirus NL63 neutralization activity was analyzed with pseudotyped lentiviral vectors. Results The severity of COVID-19 increased with age, and male patients encountered more serious symptoms than female patients. Disease severity was correlated with the amount of SARS-CoV-2–specific immunoglobulin (Ig) G and IgA and the neutralization activity of the antibodies. The amount of SARS-CoV-2–specific IgG antibodies decreased with time after polymerase chain reaction conformation of the infection, and antibodies directed against the nucleoprotein waned faster than spike protein-directed antibodies. In contrast, for the common flu coronavirus NL63, COVID-19 disease severity seemed to be correlated with low NL63-neutralizing activities, suggesting the possibility of cross-reactive protection. Conclusion The results describe the humoral immune responses against SARS-CoV-2 and might aid the identification of correlates of protection needed for vaccine development.


Author(s):  
Celia Boukadida ◽  
Blanca Taboada ◽  
Marina Escalera-Zamudio ◽  
Pavel Isa ◽  
José Ernesto Ramírez-González ◽  
...  

The genetic association of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) with different clinical conditions remains unclear and needs further investigation. In this study, we characterized 57 complete SARS-CoV-2 genomes from patients in Mexico with distinct disease severity outcomes: mild disease or ambulatory care, severe disease or hospitalized, and deceased.


Author(s):  
Yiqi Ruben Luo ◽  
Indrani Chakraborty ◽  
Cassandra Yun ◽  
Alan H B Wu ◽  
Kara L Lynch

Abstract The kinetics of IgG avidity maturation during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was studied. The IgG avidity assay, using a novel label-free immunoassay technology, revealed a strong correlation between IgG avidity and days since symptom onset. Peak readings were significantly higher in severe than mild disease cases.


Author(s):  
F. Ouyang ◽  
D. A. Ray ◽  
O. L. Krivanek

Electron backscattering Kikuchi diffraction patterns (BKDP) reveal useful information about the structure and orientation of crystals under study. With the well focused electron beam in a scanning electron microscope (SEM), one can use BKDP as a microanalysis tool. BKDPs have been recorded in SEMs using a phosphor screen coupled to an intensified TV camera through a lens system, and by photographic negatives. With the development of fiber-optically coupled slow scan CCD (SSC) cameras for electron beam imaging, one can take advantage of their high sensitivity and wide dynamic range for observing BKDP in SEM.We have used the Gatan 690 SSC camera to observe backscattering patterns in a JEOL JSM-840A SEM. The CCD sensor has an active area of 13.25 mm × 8.83 mm and 576 × 384 pixels. The camera head, which consists of a single crystal YAG scintillator fiber optically coupled to the CCD chip, is located inside the SEM specimen chamber. The whole camera head is cooled to about -30°C by a Peltier cooler, which permits long integration times (up to 100 seconds).


Author(s):  
N. Mori ◽  
T. Oikawa ◽  
Y. Harada ◽  
J. Miyahara ◽  
T. Matsuo

The Imaging Plate (IP) is a new type imaging device, which was developed for diagnostic x ray imaging. We have reported that usage of the IP for a TEM has many merits; those are high sensitivity, wide dynamic range, and good linearity. However in the previous report the reading system was prototype drum-type-scanner, and IP was also experimentally made, which phosphor layer was 50μm thick with no protective layer. So special care was needed to handle them, and they were used only to make sure the basic characteristics. In this article we report the result of newly developed reading, printing system and high resolution IP for practical use. We mainly discuss the characteristics of the IP here. (Precise performance concerned with the reader and other system are reported in the other article.)Fig.1 shows the schematic cross section of the IP. The IP consists of three parts; protective layer, phosphor layer and support.


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