scholarly journals Serological Analysis Reveals an Imbalanced IgG Subclass Composition Associated with COVID-19 Disease Severity

2020 ◽  
Author(s):  
Jennifer L. Yates ◽  
Dylan J. Ehrbar ◽  
Danielle T. Hunt ◽  
Roxanne C. Girardin ◽  
Alan Dupuis ◽  
...  
Keyword(s):  
Disease Severity ◽  
Wide Spectrum ◽  
Severe Disease ◽  
Neutralizing Antibody ◽  
Igg Subclass ◽  
Serological Analysis ◽  
Serum Samples ◽  
Plasma Therapy ◽  
Igg3 Subclass ◽  
Antibody Levels

SummaryCOVID-19 is associated with a wide spectrum of disease severity, ranging from asymptomatic to acute respiratory distress syndrome (ARDS). Paradoxically, a direct relationship has been suggested between COVID-19 disease severity, and the levels of circulating SARS-CoV-2-specific antibodies, including virus neutralizing titers. Through a serological analysis of serum samples from 536 convalescent healthcare workers, we found that SARS-CoV-2-specific and virus-neutralizing antibody levels were indeed elevated in individuals that experienced severe disease. The severity-associated increase in SARS-CoV-2-specific antibody was dominated by IgG, with an IgG subclass ratio skewed towards elevated receptor binding domain (RBD)- and S1-specific IgG3. However, RBD- and S1-specific IgG1, rather than IgG3 were best correlated with virus-neutralizing titers. We propose that Spike-specific IgG3 subclass utilization contributes to COVID-19 disease severity through potent Fc-mediated effector functions. These results have significant implications for SARS-CoV-2 vaccine design, and convalescent plasma therapy.

scholarly journals Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio and Their Role as Predictors of Disease Severity of Coronavirus Disease 2019 (COVID-19)

2021 ◽  
Author(s):  
Rohit Jain ◽  
Arun Gopal ◽  
Basant Kumar Pathak ◽  
Sourya Sourabh Mohakuda ◽  
TVSVGK Tilak ◽  
...  
Keyword(s):  
Disease Severity ◽  
Complete Blood Count ◽  
Wide Spectrum ◽  
Statistical Significance ◽  
Severe Disease ◽  
Neutrophil To Lymphocyte Ratio ◽  
Screening Tools ◽  
Platelet To Lymphocyte Ratio ◽  
Lymphocyte Ratio ◽  
Time Of Admission

Abstract Context Due to the wide spectrum of clinical illness in coronavirus disease 2019 (COVID-19) patients, it is important to stratify patients into severe and nonsevere categories. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been evaluated rapidly by a few studies worldwide for its association with severe disease, but practically none have been conducted in the Indian population. This study was undertaken to examine the role of NLR and PLR in predicting severe disease in Indian patients. Objectives The objective was to study the association of NLR and PLR observed at the time of admission with maximum disease severity during hospitalization and to study their role in predicting disease severity. Material and Methods A total of 229 COVID-19 patients were admitted at the center during the study period. After applying inclusion and exclusion criteria, 191 patients were included in the study. The demographic, clinical, and laboratory (complete blood count, NLR, and PLR) data of all patients were obtained at the time of admission. Maximum disease severity of all patients was assessed during hospitalization. Statistical Analysis Chi-square and Mann–Whitney U tests were used to assess statistical significance. Receiver operating characteristic curve (ROC) was plotted for NLR and PLR to estimate the cutoff values and sensitivity and specificity using Youden’s index for predicting severe disease. Logistic regression analysis was used to estimate the odds ratios (OR) and 95% confidence intervals. Results Mean NLR and PLR were significantly higher in severe patients (NLR = 7.41; PLR = 204) compared with nonsevere patients (NLR = 3.30; PLR = 121). ROC analysis showed that NLR, in comparison to PLR, had a higher area under the curve (AUC) of 0.779, with a larger OR of 1.237 and cutoff of 4.1, and showed 69% sensitivity and 78% specificity in predicting severe disease. Cut off for PLR was 115.3, which showed 79% sensitivity and 62% specificity in predicting severe disease. Conclusion NLR and PLR, both showing acceptable AUCs, can be used as screening tools to predict disease severity. However, NLR was a better predictor of disease severity.

scholarly journals Dynamic Alterations of Anti-S-Protein Igg Subclasses and of Th1/Th2 Responses are Hallmarks of Acute Severe COVID-19 Disease

2021 ◽  
Author(s):  
Yun Shan Goh ◽  
Siew-Wai Fong ◽  
Siti Naqiah Amrun ◽  
Cheryl Lee ◽  
Pei Xiang Hor ◽  
...  
Keyword(s):  
Disease Severity ◽  
Severe Disease ◽  
Th2 Response ◽  
S Protein ◽  
Th1 Response ◽  
Humoral Immune ◽  
Mild Disease ◽  
Humoral Immune Responses ◽  
Disease Spectrum ◽  
Antibody Levels

Abstract PurposeCOVID-19, caused by Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2), has a wide disease spectrum ranging from asymptomatic to severe. While it is widely accepted that specific humoral immune responses are critical in controlling the infection, the relationship between the humoral immune response and disease severity is currently unclear.MethodsUsing a flow cytometry-based assay to detect specific antibodies against full length S protein, we compared the antibody levels between patients from different severity groups. We also analysed the cytokine profiles of patients from different severity groups by multiplex microbead-based immunoassay.ResultsWe found an association between specific IgM, IgA and IgG against the spike protein and disease severity. By comparing the ratio of Th1 IgG1 and IgG3 to Th2 IgG2 and IgG4, we observed that all severity groups exhibited a ratio that was skewed towards a stronger Th1 response over Th2 response. In addition to the strong Th1 response, patients with severe disease also developed a Th2 response, as exemplified by the smaller ratio of IgG1 and IgG3 over IgG2 and IgG4 and the smaller Th1/Th2 cytokine ratios, compared to patients with mild disease severity. ConclusionThe results suggest that acute severity or disease resolution is associated with a specific immunological phenotype. A smaller skew towards a Th1 response over Th2 response, during infection, may contribute to disease progression, while a greater skew towards a Th1 response over Th2 response may contribute to a better disease outcome. This may suggest potential therapeutic approaches to COVID-19 disease management.

scholarly journals Differential Association of Viral Dynamics With Disease Severity Depending on Patients’ Age Group in COVID-19

2021 ◽  
Vol 12 ◽  
Author(s):  
Yuri Kim ◽  
Shinhyea Cheon ◽  
Hyeongseok Jeong ◽  
Uni Park ◽  
Na-Young Ha ◽  
...  
Keyword(s):  
Viral Load ◽  
Elderly Patients ◽  
Disease Severity ◽  
Acute Phase ◽  
Inflammatory Responses ◽  
Severe Disease ◽  
Neutralizing Antibody ◽  
The Elderly ◽  
Clinical Severity ◽  
Younger Patients

Despite a clear association of patient’s age with COVID-19 severity, there has been conflicting data on the association of viral load with disease severity. Here, we investigated the association of viral load dynamics with patient’s age and severity of COVID-19 using a set of respiratory specimens longitudinally collected (mean: 4.8 times/patient) from 64 patients with broad distribution of clinical severity and age during acute phase. Higher viral burden was positively associated with inflammatory responses, as assessed by IL-6, C-reactive protein, and lactate dehydrogenase levels in patients’ plasma collected on the same day, primarily in the younger cohort (≤59 years old) and in mild cases of all ages, whereas these were barely detectable in elderly patients (≥60 years old) with critical disease. In addition, viral load dynamics in elderly patients were not significantly different between mild and critical cases, even though more enhanced inflammation was consistently observed in the elderly group when compared to the younger group during the acute phase of infection. The positive correlation of viral load with disease severity in younger patients may explain the increased therapeutic responsiveness to current antiviral drugs and neutralizing antibody therapies in younger patients compared to elderly patients. More careful intervention against aging-associated inflammation might be required to mitigate severe disease progression and reduce fatality in COVID-19 patients more than 60 years old.

scholarly journals Detection, prevalence, and duration of humoral responses to SARS-CoV-2 under conditions of limited population exposure.

2020 ◽  
Author(s):  
Tyler J Ripperger ◽  
Jennifer L Uhrlaub ◽  
Makiko Watanabe ◽  
Rachel Wong ◽  
Yvonne Castaneda ◽  
...  
Keyword(s):  
Local Community ◽  
Severe Disease ◽  
Neutralizing Antibody ◽  
Population Level ◽  
Population Exposure ◽  
Antibody Titers ◽  
Asymptomatic Individuals ◽  
Humoral Responses ◽  
Antibody Levels ◽  
Antibody Kinetics

We conducted an extensive serological study to quantify population-level exposure and define correlates of immunity against SARS-CoV-2. We found that relative to mild COVID-19 cases, individuals with severe disease exhibited elevated authentic virus-neutralizing titers and antibody levels against nucleocapsid (N) and the receptor binding domain (RBD) and the S2 region of spike protein. Unlike disease severity, age and sex played lesser roles in serological responses. All cases, including asymptomatic individuals, seroconverted by 2 weeks post-PCR confirmation. RBD- and S2-specific and neutralizing antibody titers remained elevated and stable for at least 2-3 months post-onset, whereas those against N were more variable with rapid declines in many samples. Testing of 5882 self-recruited members of the local community demonstrated that 1.24% of individuals showed antibody reactivity to RBD. However, 18% (13/73) of these putative seropositive samples failed to neutralize authentic SARS-CoV-2 virus. Each of the neutralizing, but only 1 of the non-neutralizing samples, also displayed potent reactivity to S2. Thus, inclusion of multiple independent assays markedly improved the accuracy of antibody tests in low seroprevalence communities and revealed differences in antibody kinetics depending on the viral antigen. In contrast to other reports, we conclude that immunity is durable for at least several months after SARS-CoV-2 infection.

Neutralizing antibody titers six months after Comirnaty vaccination: kinetics and comparison with SARS-CoV-2 immunoassays

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Andrea Padoan ◽  
Chiara Cosma ◽  
Francesco Bonfante ◽  
Foscarina della Rocca ◽  
Francesco Barbaro ◽  
...  
Keyword(s):  
Vaccine Dose ◽  
Neutralizing Antibody ◽  
University Hospital ◽  
Serum Samples ◽  
Viral Neutralization ◽  
Previous Infection ◽  
Antibody Titers ◽  
Males And Females ◽  
Antibody Levels

Abstract Objectives mRNA vaccines, including Comirnaty (BNT162b2 mRNA, BioNTech-Pfizer), elicit high IgG and neutralizing antibody (NAb) responses after the second dose, but the progressive decrease in serum antibodies against SARS-CoV-2 following vaccination have raised questions concerning long-term immunity, decreased antibody levels being associated with breakthrough infections after vaccination, prompting the consideration of booster doses. Methods A total number of 189 Padua University-Hospital healthcare workers (HCW) who had received a second vaccine dose were asked to collect serum samples for determining Ab at 12 (t12) and 28 (t28) days, and 6 months (t6m) after their first Comirnaty/BNT162b2 inoculation. Ab titers were measured with plaque reduction neutralization test (PRNT), and three chemiluminescent immunoassays, targeting the receptor binding domain (RBD), the trimeric Spike protein (trimeric-S), and surrogate viral neutralization tests (sVNT). Results The median percentages (interquartile range) for decrease in antibodies values 6 months after the first dose were 86.8% (67.1–92.8%) for S-RBD IgG, 82% (58.6–89.3%) for trimeric-S, 70.4% (34.5–86.4%) for VNT-Nab, 75% (50–87.5%) for PRNT50 and 75% (50–93.7%) for PRNT90. At 6 months, neither PRNT titers nor VNT-Nab and S-RBD IgG bAb levels correlated with age (p=0.078) or gender (p=0.938), while they were correlated with previous infection (p<0.001). Conclusions After 6 months, a method-independent reduction of around 90% in anti-SARS-CoV-2 antibodies was detected, while no significant differences were found between values of males and females aged between 24 and 65 years without compromised health status. Further efforts to improve analytical harmonization and standardization are needed.

scholarly journals A tetravalent live attenuated dengue virus vaccine stimulates balanced immunity to multiple serotypes in humans

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Usha K. Nivarthi ◽  
Jesica Swanstrom ◽  
Matthew J. Delacruz ◽  
Bhumi Patel ◽  
Anna P. Durbin ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Dengue Virus ◽  
Vaccine Development ◽  
Severe Disease ◽  
Neutralizing Antibody ◽  
Post Challenge ◽  
Serum Samples ◽  
Denv Serotypes ◽  
Vaccine Component ◽  
Sterilizing Immunity

AbstractThe four-dengue virus (DENV) serotypes infect several hundred million people annually. For the greatest safety and efficacy, tetravalent DENV vaccines are designed to stimulate balanced protective immunity to all four serotypes. However, this has been difficult to achieve. Clinical trials with a leading vaccine demonstrated that unbalanced replication and immunodominance of one vaccine component over others can lead to low efficacy and vaccine enhanced severe disease. The Laboratory of Infectious Diseases at the National Institutes of Health has developed a live attenuated tetravalent DENV vaccine (TV003), which is currently being tested in phase 3 clinical trials. Here we report, our study to determine if TV003 stimulate balanced and serotype-specific (TS) neutralizing antibody (nAb) responses to each serotype. Serum samples from twenty-one dengue-naive individuals participated under study protocol CIR287 (ClinicalTrials.gov NCT02021968) are analyzed 6 months after vaccination. Most subjects (76%) develop TS nAbs to 3 or 4 DENV serotypes, indicating immunity is induced by each vaccine component. Vaccine-induced TS nAbs map to epitopes known to be targets of nAbs in people infected with wild type DENVs. Following challenge with a partially attenuated strain of DENV2, all 21 subjects are protected from the efficacy endpoints. However, some vaccinated individuals develop post challenge nAb boost, while others mount post-challenge antibody responses that are consistent with sterilizing immunity. TV003 vaccine induced DENV2 TS nAbs are associated with sterilizing immunity. Our results indicate that nAbs to TS epitopes on each serotype may be a better correlate than total levels of nAbs currently used for guiding DENV vaccine development.

scholarly journals One-Step Rapid Quantification of Serum Neutralizing Antibody after COVID-19 Vaccination by a High-Throughput Nanoplasmonic Sensor Platform

2021 ◽  
Author(s):  
Liping Huang ◽  
Ying Li ◽  
Luo Changyou ◽  
Nadia Touil ◽  
Hicham el Annaz ◽  
...  
Keyword(s):  
High Throughput ◽  
Vaccine Development ◽  
Limit Of Detection ◽  
Neutralizing Antibody ◽  
Serum Samples ◽  
Igg Antibody ◽  
Plasma Therapy ◽  
One Step ◽  
The One ◽  
Rapid Quantification

ABSTRACTThe COVID-19 vaccination efficacy depends on serum production level of the neutralizing IgG antibody (NA) specific to the receptor binding domain of SARS-Cov-2 spike protein. Therefore, a high-throughput rapid assay to measure the total SARS-CoV-2 NA level is urgently needed for COVID-19 serodiagnosis, convalescent plasma therapy, vaccine development, and assessment. Here, we developed a nanoplasmonic immunosorbent assay (NanoPISA) platform for one-step rapid quantification of SARS-CoV-2 NAs in clinical serum samples for high-throughput evaluation of COVID-19 vaccine effectiveness. The NanoPISA platform enhanced by the use of nanoporous hollow gold nanoparticle coupling was able to detect SARS-CoV-2 NAs with a limit of detection of 0.1 ng/mL within 15 min. The one-step NanoPISA for SARS-CoV-2 NA detection in clinical specimens yielded good results, comparable to those obtained in the gold standard seroneutralization test and the surrogate virus neutralizing ELISA. Collectively, our findings indicate that the one-step NanoPISA may offer a rapid and high-throughput NA quantification platform for evaluating the effectiveness of COVID-19 vaccines.

scholarly journals Serological Analysis Reveals an Imbalanced IgG Subclass Composition Associated with COVID-19 Disease Severity

2021 ◽  
pp. 100329
Author(s):  
Jennifer L. Yates ◽  
Dylan J. Ehrbar ◽  
Danielle T. Hunt ◽  
Roxanne C. Girardin ◽  
Alan P. Dupuis ◽  
...  
Keyword(s):  
Disease Severity ◽  
Igg Subclass ◽  
Serological Analysis

scholarly journals Dynamics of neutralizing antibody titers in the months after SARS-CoV-2 infection

2020 ◽  
Author(s):  
Katharine HD Crawford ◽  
Adam S Dingens ◽  
Rachel Eguia ◽  
Caitlin R Wolf ◽  
Naomi Wilcox ◽  
...  
Keyword(s):  
Symptom Onset ◽  
Neutralizing Antibodies ◽  
Severe Disease ◽  
Neutralizing Antibody ◽  
Spike Protein ◽  
Early Immune Response ◽  
Antibody Titers ◽  
Antibody Levels ◽  
Time Frames ◽  
Initial Peak

Most individuals infected with SARS-CoV-2 develop neutralizing antibodies that target the viral spike protein. Here we quantify how levels of these antibodies change in the months following SARS-CoV-2 infection by examining longitudinal samples collected between ≈30 and 152 days post-symptom onset from a prospective cohort of 34 recovered individuals with asymptomatic, mild, or moderate-severe disease. Neutralizing antibody titers declined an average of about four-fold from one to four months post-symptom onset. Importantly, our data are consistent with the expected early immune response to viral infection, where an initial peak in antibody levels is followed by a decline to a lower plateau. Additional studies of long-lived B-cells and antibody titers over longer time frames are necessary to determine the durability of immunity to SARS-CoV-2.

scholarly journals Dichotomy between the humoral and cellular responses elicited by mRNA and adenoviral vector vaccines against SARS-CoV-2

2021 ◽  
Author(s):  
Rahul Ukey ◽  
Natalie Bruiners ◽  
Hridesh Mishra ◽  
Pankaj K. Mishra ◽  
Deborah McCloskey ◽  
...  
Keyword(s):  
Single Dose ◽  
Adenoviral Vector ◽  
Severe Disease ◽  
Neutralizing Antibody ◽  
Cellular Responses ◽  
Real World Data ◽  
Symptomatic Infection ◽  
Cell Responses ◽  
Binding Antibody ◽  
Antibody Levels

AbstractProtection from severe disease and hospitalization by SARS-CoV-2 vaccination has been amply demonstrated by real-world data. However, the rapidly evolving pandemic raises new concerns. One pertains efficacy of adenoviral vector-based vaccines, particularly the single-dose Ad26.COV2.S, relative to mRNA vaccines. We investigated the immunogenicity of Ad26.COV2.S and mRNA vaccines in 33 subjects vaccinated with either vaccine class five months earlier on average. After controlling for time since vaccination, Spike-binding antibody and neutralizing antibody levels were higher in the mRNA-vaccinated subjects, while no significant differences in antigen-specific B cell and T cell responses were observed between the two groups. Thus, a dichotomy exists between humoral and cellular responses elicited by the two vaccine classes. Our results have implications for the need of booster doses in vaccinated subjects and might explain the dichotomy reported between the waning protection from symptomatic infection by SARS-CoV-2 vaccination and its persisting efficacy in preventing hospitalization and death.

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