scholarly journals A multiplex chemiluminescent immunoassay for serological profiling of COVID-19-positive symptomatic and asymptomatic patients

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Allison N. Grossberg ◽  
Lilia A. Koza ◽  
Aurélie Ledreux ◽  
Chad Prusmack ◽  
Hari Krishnan Krishnamurthy ◽  
...  
Keyword(s):  
Antibody Responses ◽  
Receptor Binding Domain ◽  
Asymptomatic Patients ◽  
Returns To Work ◽  
Adults And Children ◽  
Serology Test ◽  
Chemiluminescent Immunoassay ◽  
Asymptomatic Individuals ◽  
Multiplex Serology ◽  
Insight Into

AbstractThe COVID-19 pandemic affects more than 81 million people worldwide with over 1.7 million deaths. As the population returns to work, it is critical to develop tests that reliably detect SARS-CoV-2-specific antibodies. Here we present results from a multiplex serology test for assessing the antibody responses to COVID-19. In an initial large cohort, this test shows greater than 99% agreement with COVID-19 PCR test. In a second outpatient cohort consisting of adults and children in Colorado, the IgG responses are more robust in positive/symptomatic participants than in positive/asymptomatic participants, the IgM responses in symptomatic participants are transient and largely fall below the detection limit 30 days after symptom onset, and the levels of IgA against SARS-CoV-2 receptor binding domain are significantly increased in participants with moderate-to-severe symptoms compared to those with mild-to-moderate symptoms or asymptomatic individuals. Our results thus provide insight into serology profiling and the immune response to COVID-19.

scholarly journals Serology profile and effects of influenza vaccination on COVID-19-positive symptomatic and asymptomatic patients

2020 ◽  
Author(s):  
Allison N. Grossberg ◽  
Lilia A. Koza ◽  
Aurelie Ledreux ◽  
Chad Prusmack ◽  
Hari Krishnan Krishnamurthy ◽  
...  
Keyword(s):  
Immune Response ◽  
Detection Limit ◽  
Influenza Vaccination ◽  
Specific Antibodies ◽  
Asymptomatic Patients ◽  
Returns To Work ◽  
Adults And Children ◽  
Serology Test ◽  
Multiplex Serology ◽  
Insight Into

Abstract The COVID-19 pandemic has affected more than 6.6 million people worldwide. As the population returns to work, it is critical to develop tests that can reliably detect SARS-CoV-2-specific antibodies. Here, we present the results of a novel multiplex serology test to assess the immune response to COVID-19 in an outpatient cohort consisting of adults and children in Colorado. The IgG response was more robust in positive/symptomatic participants than in positive/asymptomatic participants. The IgM response in symptomatic participants was transient and largely fell below the detection limit 30 days after symptom onset. Influenza vaccination gave rise to milder symptomology, but did not protect against contagion. These results provide novel insight into serology profiling and the immune response to COVID-19.

scholarly journals Anti–SARS-CoV-2 Antibody Responses in Convalescent Plasma Donors Are Increased in Hospitalized Patients; Subanalyses of a Phase 2 Clinical Study

2020 ◽  
Vol 8 (12) ◽  
pp. 1885 ◽  
Author(s):  
Evangelos Terpos ◽  
Marianna Politou ◽  
Theodoros N. Sergentanis ◽  
Andreas Mentis ◽  
Margherita Rosati ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Multiplex Assay ◽  
Hospitalized Patients ◽  
Antibody Responses ◽  
Receptor Binding Domain ◽  
Phase 2 ◽  
N Protein ◽  
Asymptomatic Patients ◽  
Antibody Isotypes ◽  
Antibody Titers

We evaluated the antibody responses in 259 potential convalescent plasma donors for Covid-19 patients. Different assays were used: a commercial ELISA detecting antibodies against the recombinant spike protein (S1); a multiplex assay detecting total and specific antibody isotypes against three SARS-CoV-2 antigens (S1, basic nucleocapsid (N) protein and receptor-binding domain (RBD)); and an in-house ELISA detecting antibodies to complete spike, RBD and N in 60 of these donors. Neutralizing antibodies (NAb) were also evaluated in these 60 donors. Analyzed samples were collected at a median time of 62 (14–104) days from the day of first symptoms or positive PCR (for asymptomatic patients). Anti-SARS-CoV-2 antibodies were detected in 88% and 87.8% of donors using the ELISA and the multiplex assay, respectively. The multivariate analysis showed that age ≥50 years (p < 0.001) and need for hospitalization (p < 0.001) correlated with higher antibody titers, while asymptomatic status (p < 0.001) and testing >60 days after symptom onset (p = 0.001) correlated with lower titers. Interestingly, pseudotype virus-neutralizing antibodies (PsNAbs) significantly correlated with spike and with RBD antibodies by ELISA. Sera with high PsNAb also showed a strong ability to neutralize active SARS-CoV-2 virus, with hospitalized patients showing higher titers. Therefore, convalescent plasma donors can be selected based on the presence of high RBD antibody titers.

scholarly journals SARS-CoV-2 Antibody Responses Correlate with Resolution of RNAemia But Are Short-Lived in Patients with Mild Illness

2020 ◽  
Author(s):  
Katharina Röltgen ◽  
Oliver F Wirz ◽  
Bryan A Stevens ◽  
Abigail E Powell ◽  
Catherine A Hogan ◽  
...  
Keyword(s):  
Protective Immunity ◽  
Antibody Responses ◽  
Receptor Binding Domain ◽  
Plasma Samples ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Specific Antibodies ◽  
Immune Clearance ◽  
Humoral Immune ◽  
Asymptomatic Individuals

SARS-CoV-2-specific antibodies, particularly those preventing viral spike receptor binding domain (RBD) interaction with host angiotensin-converting enzyme 2 (ACE2) receptor, could offer protective immunity, and may affect clinical outcomes of COVID-19 patients. We analyzed 625 serial plasma samples from 40 hospitalized COVID-19 patients and 170 SARS-CoV-2-infected outpatients and asymptomatic individuals. Severely ill patients developed significantly higher SARS-CoV-2-specific antibody responses than outpatients and asymptomatic individuals. The development of plasma antibodies was correlated with decreases in viral RNAemia, consistent with potential humoral immune clearance of virus. Using a novel competition ELISA, we detected antibodies blocking RBD-ACE2 interactions in 68% of inpatients and 40% of outpatients tested. Cross-reactive antibodies recognizing SARS-CoV RBD were found almost exclusively in hospitalized patients. Outpatient and asymptomatic individuals' serological responses to SARS-CoV-2 decreased within 2 months, suggesting that humoral protection may be short-lived.

scholarly journals Defining the features and duration of antibody responses to SARS-CoV-2 infection associated with disease severity and outcome

2020 ◽  
Vol 5 (54) ◽  
pp. eabe0240 ◽  
Author(s):  
Katharina Röltgen ◽  
Abigail E. Powell ◽  
Oliver F. Wirz ◽  
Bryan A. Stevens ◽  
Catherine A. Hogan ◽  
...  
Keyword(s):  
Acute Illness ◽  
Antibody Responses ◽  
Serological Response ◽  
Receptor Binding Domain ◽  
Igg Antibodies ◽  
Angiotensin Converting Enzyme 2 ◽  
Inpatient Outcomes ◽  
Plasma Antibody ◽  
Longitudinal Plasma ◽  
Asymptomatic Individuals

SARS-CoV-2-specific antibodies, particularly those preventing viral spike receptor binding domain (RBD) interaction with host angiotensin-converting enzyme 2 (ACE2) receptor, can neutralize the virus. It is, however, unknown which features of the serological response may affect clinical outcomes of COVID-19 patients. We analyzed 983 longitudinal plasma samples from 79 hospitalized COVID-19 patients and 175 SARS-CoV-2-infected outpatients and asymptomatic individuals. Within this cohort, 25 patients died of their illness. Higher ratios of IgG antibodies targeting S1 or RBD domains of spike compared to nucleocapsid antigen were seen in outpatients who had mild illness versus severely ill patients. Plasma antibody increases correlated with decreases in viral RNAemia, but antibody responses in acute illness were insufficient to predict inpatient outcomes. Pseudovirus neutralization assays and a scalable ELISA measuring antibodies blocking RBD-ACE2 interaction were well correlated with patient IgG titers to RBD. Outpatient and asymptomatic individuals’ SARS-CoV-2 antibodies, including IgG, progressively decreased during observation up to five months post-infection.

scholarly journals Naturally acquired antibody kinetics against Plasmodium vivax antigens in people from a low malaria transmission region in western Thailand

2021 ◽  
Author(s):  
Zoe Shih-Jung Liu ◽  
Jetsumon Sattabongkot ◽  
Michael White ◽  
Sadudee Chotirat ◽  
Chalermpon Kumpitak ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Antibody Responses ◽  
Symptomatic Infection ◽  
Low Transmission ◽  
Luminex Assay ◽  
Asymptomatic Patients ◽  
Populations At Risk ◽  
Transmission Region ◽  
Asymptomatic Individuals ◽  
Antibody Kinetics

Plasmodium vivax is the dominant Plasmodium spp. causing the disease malaria in low-transmission regions outside of Africa. These regions often feature high proportions of asymptomatic patients with sub-microscopic parasitaemia and relapses. Naturally acquired antibody responses are induced after Plasmodium infection, providing partial protection against high parasitaemia and clinical episodes. However, previous work has failed to address the presence and maintenance of such antibody responses to P. vivax particularly in low-transmission regions. We followed 34 patients in western Thailand after symptomatic P. vivax infections to monitor antibody kinetics over 9 months, during which no recurrent infections occurred. We assessed total IgG, IgG subclass and IgM levels to up to 52 P. vivax proteins every 2-4 weeks using a multiplexed Luminex assay, and identified protein-specific variation in antibody longevity. Generally, an increase in antibody level was observed within 1-week post symptomatic infection, followed by an exponential decay of different rates. We observed mostly IgG1 dominance and IgG3 sub-dominance in this population. IgM responses followed similar kinetic patterns to IgG, with some proteins unexpectedly inducing long-lived IgM responses. We also monitored antibody responses against 27 IgG-immunogenic antigens in 30 asymptomatic individuals from a similar region. Our results demonstrate that most antigens induced robust and long-lived total IgG responses following asymptomatic infections in the absence of (detected) boosting infections. Our work provides new insights into the development and maintenance of naturally acquired immunity to P. vivax and will guide the potential use of serology to indicate immune status and/or identify populations at risk.

scholarly journals From Multiplex Serology to Serolomics—A Novel Approach to the Antibody Response against the SARS-CoV-2 Proteome

Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 749
Author(s):  
Julia Butt ◽  
Rajagopal Murugan ◽  
Theresa Hippchen ◽  
Sylvia Olberg ◽  
Monique van Straaten ◽  
...  
Keyword(s):  
Antibody Response ◽  
High Throughput ◽  
Large Population ◽  
High Sensitivity ◽  
Population Based ◽  
Antibody Responses ◽  
Hek293 Cells ◽  
Novel Approach ◽  
Assay Performance ◽  
Multiplex Serology

The emerging SARS-CoV-2 pandemic entails an urgent need for specific and sensitive high-throughput serological assays to assess SARS-CoV-2 epidemiology. We, therefore, aimed at developing a fluorescent-bead based SARS-CoV-2 multiplex serology assay for detection of antibody responses to the SARS-CoV-2 proteome. Proteins of the SARS-CoV-2 proteome and protein N of SARS-CoV-1 and common cold Coronaviruses (ccCoVs) were recombinantly expressed in E. coli or HEK293 cells. Assay performance was assessed in a COVID-19 case cohort (n = 48 hospitalized patients from Heidelberg) as well as n = 85 age- and sex-matched pre-pandemic controls from the ESTHER study. Assay validation included comparison with home-made immunofluorescence and commercial enzyme-linked immunosorbent (ELISA) assays. A sensitivity of 100% (95% CI: 86–100%) was achieved in COVID-19 patients 14 days post symptom onset with dual sero-positivity to SARS-CoV-2 N and the receptor-binding domain of the spike protein. The specificity obtained with this algorithm was 100% (95% CI: 96–100%). Antibody responses to ccCoVs N were abundantly high and did not correlate with those to SARS-CoV-2 N. Inclusion of additional SARS-CoV-2 proteins as well as separate assessment of immunoglobulin (Ig) classes M, A, and G allowed for explorative analyses regarding disease progression and course of antibody response. This newly developed SARS-CoV-2 multiplex serology assay achieved high sensitivity and specificity to determine SARS-CoV-2 sero-positivity. Its high throughput ability allows epidemiologic SARS-CoV-2 research in large population-based studies. Inclusion of additional pathogens into the panel as well as separate assessment of Ig isotypes will furthermore allow addressing research questions beyond SARS-CoV-2 sero-prevalence.

scholarly journals The First Harmonic of Radial Pulse as an Early Predictor of Silent Coronary Artery Disease and Adverse Cardiac Events in Type 2 Diabetic Patients

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Chi-Wei Chang ◽  
Kuo-meng Liao ◽  
Yi-Ting Chang ◽  
Sheng-Hung Wang ◽  
Ying-chun Chen ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Hazard Ratio ◽  
Radial Pulse ◽  
Cardiac Events ◽  
Asymptomatic Patients ◽  
Adverse Cardiac Events ◽  
Silent Coronary Artery Disease ◽  
Artery Disease ◽  
Asymptomatic Individuals

Background. It has been reported that harmonics of radial pulse is related to coronary artery disease (CAD) in patients with type 2 diabetes mellitus (T2DM). It is still unclear whether or not the first harmonics of the radial pulse spectrum is an early independent predictor of silent coronary artery disease (SCAD) and adverse cardiac events (ACE). Objectives. To measure the risk of SCAD in patients with T2DM and also to survey whether or not an increment of the first harmonic (C1) of the radial pulse increases ACE. Methods. 1968 asymptomatic individuals with T2DM underwent radial pulse wave measurement. First harmonic of the radial pressure wave, C1, was calculated. Next, the new occurrence of ACE and the new symptoms and signs of coronary artery disease were recorded. The follow-up period lasted for 14.7 ± 3.5 months. Results. Out of 1968 asymptomatic individuals with T2DM, ACE was detected in 239 (12%) of them during the follow-up period. The logrank test demonstrated that the cumulative incidence of ACE in patients with C1 above 0.96 was greater than that in those patients with C1 below 0.89 (P<0.01). By comparing the data of patients with C1 smaller than the first quartile and the patients with C1 greater than the third quartile, the hazard ratios were listed as follows: ACE (hazard ratio, 2.29; 95% CI, 1.55–3.37), heart failure (hazard ratio, 2.22; 95% CI, 1.21–4.09), myocardial infarction (hazard ratio, 2.44; 95% CI, 1.51–3.93), left ventricular dysfunction (Hazard ratio, 2.01; 95% CI, 0.86–4.70), and new symptoms and signs for coronary artery disease (hazard ratio, 2.03; 95% CI, 1.45–2.84). As C1 increased, the risk for composite ACE (P<0.001 for trend) and for coronary disease (P<0.001 for trend) also increased. The hazard ratio and trend for cardiovascular-cause mortality were not significant. Conclusions. This study showed that C1 of the radial pulse wave is correlated with cardiovascular events. Survival analysis showed that C1 value is an independent predictor of ACE and SCAD in asymptomatic patients with T2DM. Thus, screening for the first harmonic of the radial pulse may improve the risk stratification of cardiac events and SCAD in asymptomatic patients although they had no history of coronary artery disease or angina-related symptom.

scholarly journals Differential Kinetics of Cycle Threshold Values during Admission by Symptoms among Patients with Mild COVID-19: A Prospective Cohort Study

2021 ◽  
Vol 18 (15) ◽  
pp. 8181
Author(s):  
Teppei Sakano ◽  
Mitsuyoshi Urashima ◽  
Hiroyuki Takao ◽  
Kohei Takeshita ◽  
Hiroe Kobashi ◽  
...  
Keyword(s):  
Cohort Study ◽  
Viral Load ◽  
Prospective Cohort Study ◽  
Prospective Cohort ◽  
Polymerase Chain Reaction Test ◽  
Cycle Threshold ◽  
Viral Loads ◽  
Asymptomatic Patients ◽  
Asymptomatic Individuals ◽  
Chain Reaction Test

In the coronavirus disease 2019 (COVID-19) pandemic, more than half of the cases of transmission may occur via asymptomatic individuals, which makes it difficult to contain. However, whether viral load in the throat during admission is different between asymptomatic and symptomatic patients is not well known. By conducting a prospective cohort study of patients with asymptomatic or mild COVID-19, cycle threshold (Ct) values of the polymerase chain reaction test for COVID-19 were examined every other day during admission. The Ct values during admission increased more steadily in symptomatic patients and febrile patients than in asymptomatic patients, with significance (p = 0.01 and p = 0.004, respectively), although the Ct values as a whole were not significantly different between the two groups. Moreover, the Ct values as a whole were higher in patients with dysosmia/dysgeusia than in those without it (p = 0.02), whereas they were lower in patients with a headache than those without (p = 0.01). Patients who were IgG-positive at discharge maintained higher Ct values, e.g., more than 35, during admission than those with IgG-negative (p = 0.03). Assuming that viral load and Ct values are negatively associated, the viral loads as a whole and their changes by time may be different by symptoms and immune reaction, i.e., IgG-positive at discharge.

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