scholarly journals Antibody Response to SARS-CoV-2 Membrane Protein in Patients of the Acute and Convalescent Phase of COVID-19

2021 ◽  
Vol 12 ◽  
Author(s):  
Philipp Jörrißen ◽  
Paula Schütz ◽  
Matthias Weiand ◽  
Richard Vollenberg ◽  
Inga Marie Schrempf ◽  
...  
Keyword(s):  
Antibody Response ◽  
Acute Phase ◽  
Nucleocapsid Protein ◽  
M Protein ◽  
Plasma Samples ◽  
Convalescent Phase ◽  
Protein Encoding ◽  
Linear Epitopes ◽  
Specific Reactivity ◽  
Control Plasma

Understanding the course of the antibody response directed to individual epitopes of SARS-CoV-2 proteins is crucial for serological assays and establishment of vaccines. Twenty-one synthetic peptides were synthesized that have ten amino acids overlap and cover the complete membrane (M) protein. Plasma samples from 32 patients having acute disease and 30 patients from the convalescent phase were studied. Only peptide M01 (aa 1–20) and to a lesser extent peptide M21 (aa 201–222) showed specific reactivity as compared to historical control plasma samples. Peptide M01 was recognized by IgM- (71.9%) and IgG-specific antibodies (43.8%) during the acute phase as early as day 8 PIO. In a longitudinal analysis, a higher reactivity was observed for the IgM response directed to peptide M01 following day 20 PIO as compared to earlier time points of the acute phase. In the convalescent phase, antibody reactivity to the two M-specific peptides was significantly lower (<30% seropositivity). A fusion protein encoding major parts of RBD also showed higher rates of recognition during acute (50.0%) and lower rates in the convalescent phase (23.3%). Taken together, our results suggest that during the acute phase of COVID-19 antibodies are raised to two linear epitopes of the SARS-CoV-2 M protein, located at the very N- and C-termini, showing almost similar levels of reactivity as immunodominant linear epitopes derived from the spike and nucleocapsid protein. Anti-M is also present in the convalescent phase of COVID-19 patients, however at lower levels, with the N-terminus of the M protein as a preferred target.

scholarly journals A Nonfunctional Opsonic Antibody Response Frequently Occurs after Pneumococcal Pneumonia and Is Associated with Invasive Disease

mSphere ◽  
2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Fabian Uddén ◽  
Jonas Ahl ◽  
Nils Littorin ◽  
Kristoffer Strålin ◽  
Simon Athlin ◽  
...  
Keyword(s):  
Immune Response ◽  
Antibody Response ◽  
Acute Phase ◽  
Pneumococcal Infection ◽  
Adaptive Immune Response ◽  
Invasive Disease ◽  
Community Acquired Pneumonia ◽  
Antibody Activity ◽  
Adaptive Immune ◽  
Convalescent Phase

ABSTRACT Naturally acquired opsonic antipneumococcal antibodies are commonly found in nonvaccinated adults and confer protection against infection and colonization. Despite this, only limited data exist regarding the adaptive immune response after pneumococcal exposure. To investigate the dynamics of naturally acquired antipneumococcal immunity in relation to an episode of infection, opsonic antibody activity was studied with paired acute-phase and convalescent-phase sera obtained from 54 patients with pneumococcal community-acquired pneumonia (CAP) using an opsonophagocytic assay (OPA). Results were compared with clinical characteristics and anticapsular immunoglobulin (Ig) concentrations. Interestingly, a nonfunctional opsonic antibody response (characterized by a decreased convalescent-phase serum OPA titer compared to that of the acute-phase serum or undetectable titers in both sera) was observed in 19 (35%) patients. A nonfunctional convalescent-phase response was significantly more common among patients with invasive pneumococcal disease (i.e., bacteremia) than in patients without invasive disease (53%; P = 0.019). Remaining individuals exhibited either an increased convalescent-phase OPA titer (n = 24 [44%]) or a detectable, but unchanged, titer at both time points (n = 11 [20%]). No correlation was found between anticapsular Ig concentrations and OPA titers. Our findings indicate that an episode of pneumococcal infection may act as an immunizing event, leading to an improved antipneumococcal adaptive immune status. However, in some cases, when patients with CAP also suffer from bacteremia, a nonfunctional opsonic antibody response may occur. Furthermore, the results suggest that factors other than anticapsular Ig concentrations are important for opsonic antibody activity in serum. IMPORTANCE Numerous reports on the dynamics of antipneumococcal immunity in relation to immunization with pneumococcal vaccines and on the prevalence of naturally acquired immunity in various populations have been published. In contrast, studies on the dynamics of the humoral immune response triggered by pneumococcal infection are scarce. This study provides valuable information that will contribute to fill this knowledge gap. Our main results indicate that a functional immune response frequently fails to occur after CAP, predominantly among patients with simultaneous bacteremia.

scholarly journals Corrected and Republished from: A Nonfunctional Opsonic Antibody Response Frequently Occurs after Pneumococcal Pneumonia and Is Associated with Invasive Disease

mSphere ◽  
2020 ◽  
Vol 5 (6) ◽  
Author(s):  
Fabian Uddén ◽  
Jonas Ahl ◽  
Nils Littorin ◽  
Kristoffer Strålin ◽  
Simon Athlin ◽  
...  
Keyword(s):  
Immune Response ◽  
Antibody Response ◽  
Acute Phase ◽  
Pneumococcal Infection ◽  
Adaptive Immune Response ◽  
Invasive Disease ◽  
Community Acquired Pneumonia ◽  
Phase Response ◽  
Antibody Activity ◽  
Convalescent Phase

ABSTRACT Naturally acquired opsonic antipneumococcal antibodies are commonly found in nonvaccinated adults and confer protection against infection and colonization. Despite this, only limited data exist regarding the adaptive immune response after pneumococcal exposure. To investigate the dynamics of naturally acquired antipneumococcal immunity in relation to an episode of infection, opsonic antibody activity was studied with paired acute-phase and convalescent-phase sera obtained from 54 patients with pneumococcal community-acquired pneumonia (CAP) using an opsonophagocytic assay (OPA). Results were compared with clinical characteristics and anticapsular immunoglobulin (Ig) concentrations. Interestingly, a nonfunctional opsonic antibody response (characterized by a decreased convalescent-phase serum OPA titer compared to that of the acute-phase serum or undetectable titers in both sera) was observed in 19 (35%) patients. The remaining individuals exhibited either an increased convalescent-phase OPA titer (n  =  24 [44%]) or a detectable, but unchanged, titer at both time points (n = 11 [20%]). Invasive pneumococcal disease (i.e., bacteremia) was significantly more common among patients with a nonfunctional convalescent-phase response than in patients with other convalescent-phase responses. Anticapsular Ig concentrations were higher among patients with detectable convalescent-phase OPA titers (P = 0.003), and the greatest Ig concentration increase was observed among patients with an increased convalescent-phase response (P = 0.002). Our findings indicate that an episode of pneumococcal infection may act as an immunizing event. However, in some cases when patients with CAP also suffer from bacteremia, a nonfunctional opsonic antibody response may occur. Furthermore, the results suggest that factors other than anticapsular Ig concentrations determine opsonic antibody activity in serum. IMPORTANCE Numerous reports on the dynamics of antipneumococcal immunity in relation to immunization with pneumococcal vaccines and on the prevalence of naturally acquired immunity in various populations have been published. In contrast, studies on the dynamics of the humoral immune response triggered by pneumococcal infection are scarce. This study provides valuable information that will contribute to fill this knowledge gap. Our main results indicate that a functional immune response may fail after CAP, predominantly among patients with simultaneous bacteremia.

scholarly journals Expression Profiles of Plasma IFN Signaling-Related miRNAs (ISR-miRNAs) at the Acute and Recovery Phase of COVID-19

2021 ◽  
Author(s):  
Jing Wu ◽  
Xingxiang Liu ◽  
Jianguo Shao ◽  
Yuanyuan Zhang ◽  
Renfei Lu ◽  
...  
Keyword(s):  
Antibody Response ◽  
Acute Phase ◽  
Expression Profiles ◽  
Acute Infection ◽  
Critical Role ◽  
Recovery Phase ◽  
Healthy Controls ◽  
Plasma Samples ◽  
Igg Antibody ◽  
Expression Levels

Abstract BackgroundCoronavirus disease 2019 (COVID-19) has brought major harm and challenges to the world. Although many studies have suggested that IFN-I could affect the life cycle of the virus by regulating the expression level of microRNAs, the expression characteristics of plasma IFN-I signaling-related miRNAs at the acute and recovery phase of COVID-19 remain unclear.MethodsDemographic characteristics and fasting blood samples were collected from the acute and recovery phases of 29 COVID-19 patients and 29 healthy controls matched by age (± 5years) and gender (1:1). Expression levels of 12 IFN signaling-related miRNAs were analyzed using RT-qPCR. The receptor-binding domain (RBD) IgG antibody in the convalescent plasma samples was detected using competitive ELISA.ResultsCompared with healthy controls, patients with COVID-19 presented increased levels of miR-29b-3p (~ 5.91-fold), miR-497-5p (~ 2.28-fold), and miR-1246 (~ 7.97-fold), and decreased expression levels of miR-186-5p (~ 6.39-fold) and miR-15a-5p (~ 3.26-fold) at the acute phase of infection. However, the expression levels of miR-29b-3p and miR-1246, which significantly elevated at the acute phase, were not different between individuals at the recovery phase and healthy controls. The expression levels of miR-30b-5p, miR-497-5p, miR-409-3p and miR-548c-5p in convalescent plasma samples were significantly lower than those in healthy controls. However, the concentration of miR-186-5p in the convalescent plasma samples was significantly higher than that in healthy controls and patients with acute infection. Furthermore, competitive ELISA results showed that the plasma level of miR-497-5p at the acute phase positively correlated with RBD-IgG antibody response (r=0.48, P=0.038).ConclusionsThe present study firstly reported that timely and appropriate regulation of IFN signaling-related miRNA expression plays a critical role during both acute and recovery phase of SARS-CoV-2 infection. Furthermore, the circulating miR-497-5p level was positively correlated to RBD-IgG antibody response in COVID-19 patients.

scholarly journals Antibody response in COVID-19 patients with and without re-positive RT-PCR results during the convalescent phase

2021 ◽  
Author(s):  
Jing Peng ◽  
Zhi-Yong Liu ◽  
Xiao-Juan Yu ◽  
Xiao-Yan Chen ◽  
Kai Zhang ◽  
...  
Keyword(s):  
Antibody Response ◽  
Rt Pcr ◽  
Convalescent Phase

scholarly journals Intimal thickening and disruption of the media occur in the arterial walls of coronary arteries not associated with coronary arterial aneurysms in patients with Kawasaki disease

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Tomoya Tsuchihashi ◽  
Nobuyuki Kakimoto ◽  
Takashi Takeuchi ◽  
Tomohiro Suenaga ◽  
Takayuki Suzuki ◽  
...  
Keyword(s):  
Kawasaki Disease ◽  
Acute Phase ◽  
Coronary Arteries ◽  
Structural Changes ◽  
Artery Aneurysm ◽  
Intimal Thickening ◽  
Structure Damage ◽  
Convalescent Phase ◽  
Arterial Structure ◽  
The Media

Abstract Background Coronary artery aneurysm (CAA) is an important complication of Kawasaki disease (KD) that is associated with arterial structure damage. However, few studies have examined structural changes in coronary arteries that are not associated with CAA. Methods We examined coronary arteries in KD patients with CAAs who underwent follow-up coronary angiography (CAG) and optical coherence tomography (OCT). Coronary arterial branches with no abnormal findings during the most recent CAG were classified into two groups. Arteries with an acute-phase CAA that later regressed were classified as group R; arteries with no abnormal findings on either acute or convalescent phase CAG were classified as group N. Coronary arterial wall structural changes were compared between groups using OCT. Results Fifty-seven coronary arterial branches in 23 patients were evaluated by OCT. Thirty-six branches showed no abnormality during the most recent CAG. Both groups R and N comprised 18 branches. Maximum intimal thicknesses in groups R and N were 475 and 355 µm, respectively (p = 0.007). The incidences of media disruption were 100% and 67%, respectively (p = 0.02). Calcification, macrophage accumulation, and thrombus were not found in either group. Conclusions Intimal thickening and disruption of the media occur in coronary arteries with acute phase CAAs that later regress in the convalescent phase, as well as in arteries with normal CAG findings in the acute and convalescent phases.

scholarly journals Immunological imprinting of the antibody response in COVID-19 patients

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Teresa Aydillo ◽  
Alexander Rombauts ◽  
Daniel Stadlbauer ◽  
Sadaf Aslam ◽  
Gabriela Abelenda-Alonso ◽  
...  
Keyword(s):  
Immune Response ◽  
Severe Acute Respiratory Syndrome ◽  
Antibody Response ◽  
Humoral Immune Response ◽  
Nucleocapsid Protein ◽  
Spike Protein ◽  
Ongoing Research ◽  
Variable Regions ◽  
Humoral Immune ◽  
Human Coronaviruses

AbstractIn addition to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), humans are also susceptible to six other coronaviruses, for which consecutive exposures to antigenically related and divergent seasonal coronaviruses are frequent. Despite the prevalence of COVID-19 pandemic and ongoing research, the nature of the antibody response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unclear. Here we longitudinally profile the early humoral immune response against SARS-CoV-2 in hospitalized coronavirus disease 2019 (COVID-19) patients and quantify levels of pre-existing immunity to OC43, HKU1 and 229E seasonal coronaviruses, and find a strong back-boosting effect to conserved but not variable regions of OC43 and HKU1 betacoronaviruses spike protein. However, such antibody memory boost to human coronaviruses negatively correlates with the induction of IgG and IgM against SARS-CoV-2 spike and nucleocapsid protein. Our findings thus provide evidence of immunological imprinting by previous seasonal coronavirus infections that can potentially modulate the antibody profile to SARS-CoV-2 infection.

scholarly journals Viral and Immunological Characteristics of COVID-19 Vaccine Breakthrough Infections

2021 ◽  
Author(s):  
Tadaki Suzuki ◽  
Takeshi Arashiro ◽  
Takayuki Kanno ◽  
Sho Miyamoto ◽  
Shinji Saito ◽  
...  
Keyword(s):  
Acute Phase ◽  
Neutralizing Antibodies ◽  
Infectious Virus ◽  
Receptor Binding Domain ◽  
Symptom Development ◽  
Novel Mutations ◽  
Convalescent Phase ◽  
Induced Immunity ◽  
Respiratory Specimens ◽  
Host Characteristics

Abstract Since little is known about viral and host characteristics of breakthrough infections after COVID-19 vaccination, a nationwide investigation of breakthrough cases was initiated in Japan. 130 cases (90%+ received mRNA vaccines) were reported with respiratory specimens in 117 cases and sera in 68 cases. A subset of cases shed infectious virus regardless of symptom presence or viral lineages. Viral lineages for breakthrough infections matched both temporally and spatially with the circulating lineages in Japan with no novel mutations in spike receptor binding domain that may have escaped from vaccine-induced immunity were found. Anti-spike/neutralizing antibodies of breakthrough infections in the acute phase owing to vaccine-induced immunity were significantly higher than those from unvaccinated convalescent individuals but were comparable to vaccinated uninfected individuals, and followed by boosting in the convalescent phase. Symptomatic cases had low anti-spike/neutralizing antibodies in the acute phase with robust boosting in the convalescent phase, suggesting the presence of serological correlate for symptom development in COVID-19 vaccine breakthrough infections.

scholarly journals SARS-CoV-2 infection severity is linked to superior humoral immunity against the spike

2020 ◽  
Author(s):  
Jenna J. Guthmiller ◽  
Olivia Stovicek ◽  
Jiaolong Wang ◽  
Siriruk Changrob ◽  
Lei Li ◽  
...  
Keyword(s):  
Antibody Response ◽  
B Cell ◽  
Cell Response ◽  
Nucleocapsid Protein ◽  
Antigen Specificity ◽  
Memory B Cell ◽  
Reading Frame ◽  
Global Pandemic ◽  
Kinetics Of ◽  
B Cell Response

ABSTRACTSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently causing a global pandemic. The antigen specificity and kinetics of the antibody response mounted against this novel virus are not understood in detail. Here, we report that subjects with a more severe SARS-CoV-2 infection exhibit a larger antibody response against the spike and nucleocapsid protein and epitope spreading to subdominant viral antigens, such as open reading frame 8 and non-structural proteins. Subjects with a greater antibody response mounted a larger memory B cell response against the spike, but not the nucleocapsid protein. Additionally, we revealed that antibodies against the spike are still capable of binding the D614G spike mutant and cross-react with the SARS-CoV-1 receptor binding domain. Together, this study reveals that subjects with a more severe SARS-CoV-2 infection exhibit a greater overall antibody response to the spike and nucleocapsid protein and a larger memory B cell response against the spike.

Abstract 520: Acoustic Tweezing Thromboelastometry

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Daishen Luo ◽  
Damir Khismatullin ◽  
R. Glynn Holt
Keyword(s):  
Reaction Time ◽  
Whole Blood ◽  
Factor Xiii ◽  
Formation Time ◽  
Plasma Samples ◽  
Clot Strength ◽  
Plasma Coagulation ◽  
Coagulation Status ◽  
Clot Formation Time ◽  
Control Plasma

Background: Critical care patients such as trauma and major surgery patients often develop coagulopathy due to depletion of both pro- and anti-coagulants. They are at high risk of both bleeding and thrombotic complications and require monitoring of their coagulation status. The contact of a blood sample with artificial surfaces and its exposure to clot activators, which happen in all commercially available coagulation analyzers, may lead to improper assessment of blood coagulation and thus errors in predicting bleeding/thrombosis risks. Objective: Real-time assessment of whole blood or blood plasma coagulation by novel non-contact acoustic tweezing technology. Method: 4-5 microliter drops of whole blood collected from healthy volunteers or commercial control plasma were levitated in air by acoustic radiation forces. Their coagulation kinetics including reaction time, fibrin network formation time (FNFT), clot formation time and maximum clot strength was assessed from mechanical (drop shape) and photo-optical (light intensity) data. FNFT was determined as a difference between mechanical and photo-optical reaction times. Results: Whole blood samples were exposed to pro- or anti-coagulants during levitation in the acoustic tweezing device. Changes in the coagulation status between different experimental groups were detected within 10 minutes. Similarly, less than 7 minutes was required to detect significant changes in reaction time, clot formation time and maximum clot strength between low, normal, and high fibrinogen level control plasma samples. FNFT was shown to be significantly reduced in plasma samples with a higher level of Factor XIII. Conclusions: The acoustic tweezing technology integrates photo-optical tests used in plasma coagulation assays with viscoelastic tests used in whole blood analysis. Its key disruptive features are the increased reliability and accuracy due to non-contact measurement, small sample volume requirement, relatively short procedure time (<10 minutes), and the ability to assess the level of Factor XIII function from FNFT measurements. Our technology addresses a current lack of reliable methods to measure blood coagulation in patients with coagulopathy.

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